39 results on '"Quinn, Brian"'
Search Results
2. Contributors
- Author
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Abrams, Dominic J., primary, Alexander, Mark E., additional, Alexander, Peta M.A., additional, Allan, Catherine, additional, Baird, Christopher W., additional, Bergersen, Lisa, additional, Beroukhim, Rebecca, additional, Bevilacqua, Laura M., additional, Bezzerides, Vassilios, additional, Blume, Elizabeth D., additional, Breitbart, Roger E., additional, Brown, David W., additional, Callahan, Ryan, additional, Carreon, Chrystalle Katte, additional, Castellanos, Daniel A., additional, Chen, Ming Hui, additional, Cheng, Henry, additional, Colan, Steven D., additional, Daly, Kevin P., additional, de Ferranti, Sarah D., additional, del Nido, Pedro J., additional, DeWitt, Elizabeth, additional, DiNardo, James, additional, Dionne, Audrey, additional, Emani, Sitaram M., additional, Esch, Jesse J., additional, Esteso, Paul, additional, Feins, Eric N., additional, Freed, Michael D., additional, Friedman, Kevin, additional, Fulton, David R., additional, Fynn-Thompson, Francis, additional, Garbern, Jessica C., additional, Garcia-Mancebo, Julia, additional, Gauthier, Naomi, additional, Geggel, Robert L., additional, Geisser, Diana L., additional, Gellis, Laura, additional, Geva, Tal, additional, Ghbeis, Muhammad Bakr, additional, Ghelani, Sunil J., additional, Goldberg, Sarah W., additional, Gurvitz, Michelle, additional, Hames, Daniel L., additional, Harrild, David M., additional, Hartz, Jacob, additional, Hickey, Patricia, additional, Hoganson, David, additional, Jenkins, Kathy, additional, Kane, David, additional, Kaza, Aditya K., additional, Kheir, John N., additional, Kumar, R. Krishna, additional, Kwon, Michael H., additional, Lacro, Ronald V., additional, Landzberg, Michael J., additional, Lang, Peter, additional, LaRovere, Joan M., additional, Levine, Jami, additional, Lock, James Ernest, additional, Lyon, Shannon, additional, Mah, Douglas Y., additional, Marx, Gerald R., additional, Maschietto, Nicola, additional, Matte, Gregory S., additional, Mayer, John E., additional, Mills, Kimberly I., additional, Mistry, Kshitij, additional, Mullen, Mary P., additional, Nasr, Viviane G., additional, Nathan, Meena, additional, Newburger, Jane W., additional, O’Brien, Patricia, additional, O’Brien, Sharon E., additional, O’Leary, Edward T., additional, Porras, Diego, additional, Powell, Andrew J., additional, Prakash, Ashwin, additional, Pu, William T., additional, Quiat, Daniel, additional, Quinn, Brian, additional, Quinonez, Luis, additional, Rathod, Rahul H., additional, Rhodes, Jonathan, additional, Roberts, Amy E., additional, Rodriguez-Monserrate, Carla P., additional, Ronai, Christina, additional, Saia, Theresa, additional, Saleeb, Susan F., additional, Salvin, Joshua W., additional, Sanders, Stephen P., additional, Schidlow, David, additional, Shafer, Keri M., additional, Siegel, Bryan D., additional, Singh, Michael N., additional, Singh, Tajinder, additional, Teele, Sarah A., additional, Thiagarajan, Ravi R., additional, Triedman, John K., additional, Tworetzky, Wayne, additional, Valente, Anne Marie, additional, VanderPluym, Christina, additional, Walsh, Edward P., additional, Wu, Fred Ming-Chieh, additional, and Yin, Suellen, additional
- Published
- 2025
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3. The contemporary history of plastics
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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4. The emergence of plastics
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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5. Microplastic separation techniques
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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6. Microplastic identification techniques
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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7. Plastic production, waste and legislation
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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8. The interactions of microplastics and chemical pollutants
- Author
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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9. The biological impacts and effects of contaminated microplastics
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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10. Microplastic collection techniques
- Author
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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11. Microplastics, standardisation and spatial distribution
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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12. Physiochemical properties and degradation
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Crawford, Christopher Blair, primary and Quinn, Brian, additional
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- 2017
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13. Preparation and Maintenance of Live Tissues and Primary Cultures for Toxicity Studies
- Author
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Quinn, Brian, primary
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- 2014
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14. List of Contributors
- Author
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André, Chantale, primary, Auclair, Joëlle, additional, Bony, Sylvie, additional, Devaux, Alain, additional, Gagné, François, additional, Lacaze, Émilie, additional, and Quinn, Brian, additional
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- 2014
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15. Introduction
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Gagné, François, primary, André, Chantale, additional, Auclair, Joëlle, additional, Lacaze, Émilie, additional, and Quinn, Brian, additional
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- 2014
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16. Regional White Matter Volume Differences in Nondemented Aging and Alzheimer's Disease
- Author
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Salat, David, Greve, Douglas, Helmer, Karl, Buckner, Randy, Fischl, Bruce, Quinn, Brian T., and Pacheco, Jennifer
- Abstract
Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer's disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD associated volume loss that may contribute to cognitive decline., Psychology
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- 2009
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17. Repeat Repair After Translocation of an Anomalous Left Coronary Artery.
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Fernandez-Cisneros A, Feins E, Newburger J, Sekhavat S, Quinn B, and Quinonez L
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- Humans, Anomalous Left Coronary Artery surgery, Anomalous Left Coronary Artery diagnosis, Echocardiography, Transesophageal methods, Coronary Angiography, Male, Female, Cardiac Surgical Procedures methods, Coronary Vessels surgery, Coronary Vessels diagnostic imaging, Reoperation
- Abstract
We repaired a left anomalous aortic origin of coronary artery using coronary ostium translocation/reimplantation. Repeat repair was required due to suboptimal flow pattern in postoperative transesophageal echocardiography, which was confirmed with coronary angiography. We emphasize the importance of early recognition, diagnosis, and intervention to deal with a problem with the coronary repair., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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18. Dual scaffold delivery of miR-210 mimic and miR-16 inhibitor enhances angiogenesis and osteogenesis to accelerate bone healing.
- Author
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Castaño IM, Raftery RM, Chen G, Cavanagh B, Quinn B, Duffy GP, Curtin CM, and O'Brien FJ
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- Humans, Rats, Animals, Tissue Scaffolds, Bone and Bones metabolism, Tissue Engineering, Collagen, Bone Regeneration, Cell Differentiation, Osteogenesis genetics, MicroRNAs genetics, MicroRNAs metabolism
- Abstract
Angiogenesis is critical for successful bone repair, and interestingly, miR-210 and miR-16 possess counter-active targets involved in both angiogenesis and osteogenesis: miR-210 acts as an activator by silencing EFNA3 & AcvR1b, while miR-16 inhibits both pathways by silencing VEGF & Smad5. It was thus hypothesized that dual delivery of both a miR-210 mimic and a miR-16 inhibitor from a collagen-nanohydroxyapatite scaffold system may hold significant potential for bone repair. Therefore, this systems potential to rapidly accelerate bone repair by directing enhanced angiogenic-osteogenic coupling in host cells in a rat calvarial defect model at a very early 4 week timepoint was assessed. In vitro, the treatment significantly enhanced angiogenic-osteogenic coupling of human mesenchymal stem cells, with enhanced calcium deposition after just 10 days in 2D and 14 days on scaffolds. In vivo, these dual-miRNA loaded scaffolds showed more than double bone volume and vessel recruitment increased 2.3 fold over the miRNA-free scaffolds. Overall, this study demonstrates the successful development of a dual-miRNA mimic/inhibitor scaffold for enhanced in vivo bone repair for the first time, and the possibility of extending this 'off-the-shelf' platform system to applications beyond bone offers immense potential to impact a myriad of other tissue engineering areas. STATEMENT OF SIGNIFICANCE: miRNAs have potential as a new class of bone healing therapeutics as they can enhance the regenerative capacity of bone-forming cells. However, angiogenic-osteogenic coupling is critical for successful bone repair. Therefore, this study harnesses the delivery of miR-210, known to be an activator of both angiogenesis and osteogenesis, and miR-16 inhibitor, as miR-16 is known to inhibit both pathways, from a collagen-nanohydroxyapatite scaffold system to rapidly enhance osteogenesis in vitro and bone repair in vivo in a rat calvarial defect model. Overall, it describes the successful development of the first dual-miRNA mimic/inhibitor scaffold for enhanced in vivo bone repair. This 'off-the-shelf' platform system offers immense potential to extend beyond bone applications and impact a myriad of other tissue engineering areas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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19. Rapid bone repair with the recruitment of CD206 + M2-like macrophages using non-viral scaffold-mediated miR-133a inhibition of host cells.
- Author
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Castaño IM, Raftery RM, Chen G, Cavanagh B, Quinn B, Duffy GP, O'Brien FJ, and Curtin CM
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- Animals, Collagen chemistry, Drug Delivery Systems, Durapatite chemistry, Lectins, C-Type metabolism, Male, Mannose Receptor, Mannose-Binding Lectins metabolism, Mesenchymal Stem Cells drug effects, Osteogenesis drug effects, Rats, Sprague-Dawley, Receptors, Cell Surface metabolism, Antagomirs therapeutic use, Macrophages drug effects, MicroRNAs antagonists & inhibitors, Regeneration drug effects, Skull physiology, Tissue Scaffolds chemistry
- Abstract
microRNAs offer vast therapeutic potential for multiple disciplines. From a bone perspective, inhibition of miR-133a may offer potential to enhance Runx2 activity and increase bone repair. This study aims to assess the therapeutic capability of antagomiR-133a delivery from collagen-nanohydroxyapatite (coll-nHA) scaffolds following cell-free implantation in rat calvarial defects (7 mm diameter). This is, to the best of our knowledge, the first report of successful in vivo antagomiR uptake in host cells of fully immunocompetent animals without distribution to other off-target tissues. Our results demonstrate the localized release of antagomiR-133a to the implant site at 1 week post-implantation with increased calcium deposits already evident in the antagomiR-133a loaded scaffolds at this early timepoint. This was followed by an approximate 2-fold increase in bone volume versus antagomiR-free scaffolds and a significant 10-fold increase over the empty defect controls, after just 4 weeks. An increase in host CD206
+ cells suggests an accelerated pro-remodeling response by M2-like macrophages accompanying bone repair with this treatment. Overall, this non-viral scaffold-mediated antagomiR-133a delivery platform demonstrates capability to accelerate bone repair in vivo - without the addition of exogenous cells - and underlines the role of M2 macrophage-like cells in directing accelerated bone repair. Expanding the repertoire of this platform to deliver alternative miRNAs offers exciting possibilities for a variety of therapeutic indications. STATEMENT OF SIGNIFICANCE: microRNAs, small non-coding RNA molecules involved in gene regulation, may have potential as a new class of bone healing therapeutics as they can enhance the regenerative capacity of bone-forming cells. We developed a collagen-nanohydroxyapatite-microRNA scaffold system to investigate whether miR133a inhibition can enhance osteogenesis in rat MSCs and ultimately accelerate endogenous bone repair by host cells in vivo without pre-seeding cells prior to implantation. Overall, this off-the-shelf, non-viral scaffold-mediated antagomiR-133a delivery platform demonstrates capability to accelerate bone repair in vivo - without the requirement of exogenous cells - and highlights the role of CD206+ M2 macrophage-like cells in guiding accelerated bone repair. Translating the repertoire of this platform to deliver alternative miRNAs offers exciting possibilities for a vast myriad of therapeutic indications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)- Published
- 2020
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20. Microplastic accumulation in deep-sea sediments from the Rockall Trough.
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Courtene-Jones W, Quinn B, Ewins C, Gary SF, and Narayanaswamy BE
- Subjects
- Atlantic Ocean, Environmental Monitoring, Geologic Sediments, Microplastics, Plastics, Water Pollutants, Chemical analysis
- Abstract
Microplastics are widely dispersed through the marine environment. Few studies have assessed the long-term or historic prevalence of microplastics, yet acquiring such data can inform their distribution, transport and the environmental risks posed. To quantify the distribution and polymer types temporally, sediment cores were collected from >2000 m water depth in the Rockall Trough, North Atlantic Ocean. As hypothesized, a significant negative trend was observed in the frequency of microplastics with increasing sediment age, however there was an increase in polymer diversity. Microplastics were pervasive throughout the sediment analysed (10 cm depth), yet lead-210 (
210 Pb) activities were confined to the upper 4 cm, indicating this layer to be ~150 years old and thus the presence of microplastics far exceed the production of modern plastic. A number of mechanisms, including sediment reworking, could redistribute microplastics vertically. Additionally, microplastics abundance was significantly correlated with sediment porosity, suggesting interstitial transport via pore waters., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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21. The toxicity of potentially toxic elements (Cu, Fe, Mn, Zn and Ni) to the cnidarian Hydra attenuata at environmentally relevant concentrations.
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McKinley K, McLellan I, Gagné F, and Quinn B
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- Animals, Dose-Response Relationship, Drug, Estuaries, Feeding Behavior drug effects, Hydra anatomy & histology, Hydra physiology, Lethal Dose 50, Movement drug effects, Reproduction drug effects, Scotland, Toxicity Tests, Hydra drug effects, Metals, Heavy toxicity, Water Pollutants, Chemical toxicity
- Abstract
The domestic, agricultural, industrial, technological and medical applications of potentially toxic elements (PTEs) have led to global pollution in all environments. In this study, the cnidarian Hydra attenuata was exposed individually and to a mixture of 5 metals (copper, iron, manganese, zinc and nickel) at environmentally relevant concentrations (1×) within the Clyde estuary, Scotland and incremental concentrations ranging from 0.0001× to 1000×. Toxicity was investigated using morphology, attachment, hydranth number and feeding behaviour as endpoints. When exposed individually, Cu, Mn and Fe significantly reduced Hydra morphology, feeding and attachment at environmentally relevant concentrations. Hydra mortality was measured, having an LC50 of 0.045× (for the environmentally relevant mixture of metals) and Cu 0.5 mg/l, Fe 3 mg/l, Mn 2 mg/l, Zn 0.1 mg/l, Ni 0.5 mg/l for each element exposed individually. The PTE mixture incurred a significant decrease (p ≤ 0.05) in morphology at 0.0001×, with 100% mortality at 0.1× (containing a concentration of Cu 0.05 mg/l, Fe 0.3 mg/l, Mn 0.2 mg/l, Zn 0.01 mg/l, Ni 0.05 mg/l) and a toxicity threshold (TT) of 0.000005×. Both copper and iron when exposed individually to the concentration of their respective metals found in the environment resulted in 100% mortality for all Hydra exposed. These results indicate that the PTE mixture (including the individual concentrations of copper, iron, manganese and nickel) could potentially prove significantly toxic to the aquatic environment., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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22. Ecotoxicity responses of the freshwater cnidarian Hydra attenuata to 11 rare earth elements.
- Author
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Blaise C, Gagné F, Harwood M, Quinn B, and Hanana H
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- Animals, Fresh Water, Lethal Dose 50, Toxicity Tests, Hydra drug effects, Metals, Rare Earth toxicity, Water Pollutants, Chemical toxicity
- Abstract
Lanthanides are the major family of rare earth elements (REEs) owing to the essential properties these metallic species provide in diverse fields of today's world economy. They are now being mined and produced as never before. This raises new environmental concerns in terms of their expected future discharges notably to aquatic systems. Interspecies studies of their ecotoxicity are sparse and effects on aquatic life are still poorly understood. Absence of such information for cnidarians, an ecologically relevant freshwater community, thus prompted the present research on REEs toxicity using Hydra attenuata as our animal model. Lethal and sublethal ecotoxicity data generated with the 11 REEs displayed LC50 values ranging from 0.21 to 0.77 mg L
-1 and EC50 values ranging from 0.02 to 0.27 mg L-1 , thereby confirming the inherent sensitivity of Hydra to REE exposure at environmentally relevant concentrations. Additionally, two properties of REEs were shown to modulate Hydra (sub)lethal toxicity (LC50 and EC50) which decreases with increasing atomic number and with decreasing ionic radius. Compared to studies carried out with different taxonomic groups, Hydra toxicity responses to REEs proved to be among the most sensitive, along with those of other invertebrate species (i.e., Daphnia magna, Ceriodaphnia dubia, Hyalella azteca), suggesting that members of this community are likely more at risk to eventual REE discharges in aquatic environments. Demonstrated Hydra sensitivity to REE exposure strongly justifies their future use in toxicity testing battery approaches to evaluate liquid samples suspected of harbouring REEs., (Copyright © 2018. Published by Elsevier Inc.)- Published
- 2018
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23. The uptake of macroplastic & microplastic by demersal & pelagic fish in the Northeast Atlantic around Scotland.
- Author
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Murphy F, Russell M, Ewins C, and Quinn B
- Subjects
- Animals, Environmental Monitoring, Scotland, Fishes, Plastics pharmacokinetics, Water Pollutants, Chemical pharmacokinetics
- Abstract
This study reports plastic ingestion in various fish found from coastal and offshore sites in Scottish marine waters. Coastal samples consisted of three demersal flatfish species (n=128) collected from the East and West coasts of Scotland. Offshore samples consisted of 5 pelagic species and 4 demersal species (n=84) collected from the Northeast Atlantic. From the coastal fish sampled, 47.7% of the gastrointestinal tracts contained macroplastic and microplastic. Of the 84 pelagic and demersal offshore fish, only 2 (2.4%) individuals from different species had ingested plastic identified as a clear polystyrene fibre and a black polyamide fibre. The average number of plastic items found per fish from all locations that had ingested plastic was 1.8 (±1.7) with polyamide (65.3%), polyethylene terephthalate (14.4%) and acrylic (14.4%) being the three most commonly found plastics. This study adds to the existing data on macroplastic and microplastic ingestion in fish species., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2017
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24. Cortical thickness abnormalities associated with dyslexia, independent of remediation status.
- Author
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Ma Y, Koyama MS, Milham MP, Castellanos FX, Quinn BT, Pardoe H, Wang X, Kuzniecky R, Devinsky O, Thesen T, and Blackmon K
- Subjects
- Adolescent, Brain Mapping methods, Child, Female, Humans, Image Interpretation, Computer-Assisted methods, Magnetic Resonance Imaging, Male, Cerebral Cortex pathology, Dyslexia pathology
- Abstract
Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the "reading network." Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same "double hit" of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status.
- Published
- 2014
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25. Functional neuroimaging abnormalities in idiopathic generalized epilepsy.
- Author
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McGill ML, Devinsky O, Wang X, Quinn BT, Pardoe H, Carlson C, Butler T, Kuzniecky R, and Thesen T
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- Adult, Anisotropy, Brain Mapping, Diffusion Tensor Imaging, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways pathology, Neural Pathways physiopathology, Prefrontal Cortex pathology, Prefrontal Cortex physiopathology, Thalamus pathology, Thalamus physiopathology, Young Adult, Brain pathology, Brain physiopathology, Epilepsy, Generalized pathology, Epilepsy, Generalized physiopathology
- Abstract
Magnetic resonance imaging (MRI) techniques have been used to quantitatively assess focal and network abnormalities. Idiopathic generalized epilepsy (IGE) is characterized by bilateral synchronous spike-wave discharges on electroencephalography (EEG) but normal clinical MRI. Dysfunctions involving the neocortex, particularly the prefrontal cortex, and thalamus likely contribute to seizure activity. To identify possible morphometric and functional differences in the brains of IGE patients and normal controls, we employed measures of thalamic volumes, cortical thickness, gray-white blurring, fractional anisotropy (FA) measures from diffusion tensor imaging (DTI) and fractional amplitude of low frequency fluctuations (fALFF) in thalamic subregions from resting state functional MRI. Data from 27 patients with IGE and 27 age- and sex-matched controls showed similar thalamic volumes, cortical thickness and gray-white contrast. There were no differences in FA values on DTI in tracts connecting the thalamus and prefrontal cortex. Functional analysis revealed decreased fALFF in the prefrontal cortex (PFC) subregion of the thalamus in patients with IGE. We provide minimum detectable effect sizes for each measure used in the study. Our analysis indicates that fMRI-based methods are more sensitive than quantitative structural techniques for characterizing brain abnormalities in IGE.
- Published
- 2014
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26. A year-long study of the spatial occurrence and relative distribution of pharmaceutical residues in sewage effluent, receiving marine waters and marine bivalves.
- Author
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McEneff G, Barron L, Kelleher B, Paull B, and Quinn B
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- Animals, Environmental Monitoring, Pharmaceutical Preparations metabolism, Seawater chemistry, Sewage chemistry, Waste Disposal, Fluid, Water Pollutants, Chemical metabolism, Bivalvia metabolism, Pharmaceutical Preparations analysis, Wastewater chemistry, Water Pollutants, Chemical analysis
- Abstract
Reports concerning the quantitative analysis of pharmaceuticals in marine ecosystems are somewhat limited. It is necessary to determine pharmaceutical fate and assess any potential risk of exposure to aquatic species and ultimately, seafood consumers. In the work presented herein, analytical methods were optimised and validated for the quantification of pharmaceutical residues in wastewater effluent, receiving marine waters and marine mussels (Mytilus spp.). Selected pharmaceuticals included two non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac and mefenamic acid), an antibiotic (trimethoprim), an antiepileptic (carbamazepine) and a lipid regulator (gemfibrozil). This paper also presents the results of an in situ study in which caged Mytilus spp. were deployed at three sites on the Irish coastline over a 1-year period. In water samples, pharmaceutical residues were determined using solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The extraction of pharmaceuticals from mussel tissues used an additional pressurised liquid extraction (PLE) step prior to SPE and LC-MS/MS. Limits of quantification between 15 and 225 ng·L(-1) were achieved in wastewater effluent, between 3 and 38 ng·L(-1) in marine surface water and between 4 and 29 ng·g(-1) dry weight in marine mussels. Method linearity was achieved for pharmaceuticals in each matrix with correlation coefficients of R(2)≥0.976. All five selected pharmaceuticals were quantified in wastewater effluent and marine surface waters. This work has demonstrated the susceptibility of the Mytilus spp. to pharmaceutical exposure following the detection of pharmaceutical residues in the tissues of this mussel species at measurable concentrations., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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27. Seasonal variations of biomarker responses in the marine blue mussel (Mytilus spp.).
- Author
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Schmidt W, Power E, and Quinn B
- Subjects
- Animals, Biomarkers metabolism, Glutathione Transferase metabolism, Lipid Peroxidation drug effects, Oxidative Stress, Seasons, Water Pollutants, Chemical toxicity, Environmental Monitoring, Mytilus physiology
- Abstract
Biomarkers, which can detect changes at the biochemical level, have been used for many years as early warning tools in environmental monitoring. In order to distinguish between natural variability and the potential effects of anthropogenic pollution, it is essential to identify background levels and establish the potential influence of abiotic (season, temperature and salinity) and biotic (gametogenesis) factors. In this study, we examined various biomarkers of stress (glutathione S-transferase (GST)), reproduction (vitellin-like proteins) and damage (lipid peroxidation (LPO) and DNA damage (DNA)) in marine mussels (Mytilus spp.) from a known pristine hybrid zone. Levels of all biomarker expression varied between seasons and appeared to be linked to the reproductive cycle. Oxidative stress in winter, with low GST expression and a higher expression of LPO and DNA damage displayed could be explained by low food availability. These data provide vital baseline information for future ecotoxicological and environmental monitoring studies., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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28. The effect of shore location on biomarker expression in wild Mytilus spp. and its comparison with long line cultivated mussels.
- Author
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Schmidt W, O'Shea T, and Quinn B
- Subjects
- Animals, Gene Expression Regulation, Aquaculture, Biomarkers metabolism, Ecosystem, Environmental Monitoring methods, Mytilus metabolism, Stress, Physiological physiology
- Abstract
Biomarkers are a common tool in the assessment of potential effects of contaminants in aquatic organisms. In order to identify the effects of anthropogenic pollution it is essential to identify background levels and to know the range of natural variability in the biomarker response. In this study, we examined various biomarkers of stress (glutathione S-transferase and metallothionein), damage (lipid peroxidation (LPO) and DNA damage (DNA)) and reproduction (vitellin-like proteins) in marine mussels (Mytilus spp.) from four locations along a vertical transect from high to low shore and compared them with cultivated long line mussels. High shore and cultivated mussels showed significantly higher LPO and DNA damage expression than the low shore mussels indicating a level of oxidative stress resulting from mussel location. Significant effects in physiological endpoints were also found. This study highlights the need to consider the diversity of natural environmental stress factors when using biomarkers in environmental assessment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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29. Effects of the pharmaceuticals gemfibrozil and diclofenac on the marine mussel (Mytilus spp.) and their comparison with standardized toxicity tests.
- Author
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Schmidt W, O'Rourke K, Hernan R, and Quinn B
- Subjects
- Aliivibrio fischeri, Animals, Biomarkers metabolism, Glutathione Transferase metabolism, Lipid Peroxidation drug effects, Metallothionein metabolism, Mytilus, Toxicity Tests, Anti-Inflammatory Agents, Non-Steroidal toxicity, Diclofenac toxicity, Gemfibrozil toxicity, Hypolipidemic Agents toxicity, Water Pollutants, Chemical toxicity
- Abstract
Human pharmaceuticals, like the lipid lowering agent gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac are causing environmental concern. In this study, the marine mussel (Mytilus spp.) was exposed by injection to environmentally relevant and elevated (1 μg/L and 1000 μg/L) concentrations of both compounds and biomarker expression was observed. Gemfibrozil exposure induced biomarkers of stress (glutathione S-transferase and metallothionein) at both concentrations 24h and 96 h after exposure, respectively. Biomarkers of damage (lipid peroxidation (LPO) and DNA damage) were significantly affected, as well as the biomarker for reproduction, alkali-labile phosphate assay, indicating the potential oxidative stress and endocrine disrupting effect of gemfibrozil. Diclofenac significantly induced LPO after 96 h indicating tissue damage. Additionally standard toxicity tests using the marine species Vibrio fischeri, Skeletonema costatum and Tisbe battagliai showed differences in sensitivity to both drugs in the mg/L range. Results indicate a suite of tests should be used to give accurate information for regulation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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30. Evaluation of the acute, chronic and teratogenic effects of a mixture of eleven pharmaceuticals on the cnidarian, Hydra attenuata.
- Author
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Quinn B, Gagné F, and Blaise C
- Subjects
- Animal Feed, Animals, Artemia, Caffeine toxicity, Lethal Dose 50, Regeneration, Analgesics toxicity, Anti-Bacterial Agents toxicity, Feeding Behavior drug effects, Hydra drug effects, Teratogens toxicity
- Abstract
Pharmaceuticals have recently emerged as novel pollutants of potential concern in the aquatic environment where they are commonly introduced as complex mixtures via municipal effluent. In the present experiment, the freshwater cnidarian Hydra attenuata was exposed to a mixture of 11 pharmaceuticals (ibuprofen, naproxen, gemfibrozil, bezafibrate, carbamazepine, sulfapyridine, oxytetracycline, novobiocin, trimethoprim, sulfamethoxazole and caffeine) up to 10000 times (x) the concentration found in municipal effluent. Hydra regeneration and teratogenicity was measured, having an IC(50) of 781x and was found to be non teratogenic with an A/D value of approximately 1. Toxicity was investigated using both lethal (based on morphology) and sub-lethal (based on morphology, feeding behaviour, hydranth number and attachment) endpoints. The pharmaceutical mixture incurred a significant decrease in morphology at 0.1, 10 and 100x but a significant increase at 1000x. All parameters were significantly reduced at 10000x. An EC(50) of 425x and 65x based on morphology and feeding respectively and a toxicity threshold (TT) of 3.2x were calculated. When compared to the toxicity of each pharmaceutical exposed individually as previously reported [Quinn B, Gagné F, Blaise C. An investigation into the acute and chronic toxicity of eleven pharmaceuticals found in wastewater effluent on the cnidarian, H. attenuata. Sci Total Environ 2008a; 389: 306-314], the compounds in the mixture were present at concentrations 2 to 3 orders of magnitude lower for the equivalent toxicity (EC(50) and TT). These results indicate that pharmaceuticals act additively in a mixture, having sub-lethal effects at environmentally relevant (microg/L-ng/L) concentrations and that their combined concentrations could potentially prove significantly ecotoxic to Hydra and possibly to other aquatic taxa.
- Published
- 2009
- Full Text
- View/download PDF
31. The effects of pharmaceuticals on the regeneration of the cnidarian, Hydra attenuata.
- Author
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Quinn B, Gagné F, and Blaise C
- Subjects
- Algorithms, Analgesics, Non-Narcotic toxicity, Animals, Anti-Bacterial Agents toxicity, Anti-Inflammatory Agents, Non-Steroidal toxicity, Cities, Hydra metabolism, Hypolipidemic Agents toxicity, Industrial Waste, Pharmaceutical Preparations chemistry, Solvents chemistry, Toxicity Tests, Biological Assay methods, Drug-Related Side Effects and Adverse Reactions, Environmental Monitoring methods, Hydra drug effects, Water Pollutants, Chemical toxicity
- Abstract
The Hydra attenuata regeneration assay was used to identify the teratogenic potential of 10 pharmaceuticals identified in effluent from a large city wastewater treatment plant (WWTP). Three types of solvents were used to solubilise the pharmaceuticals (DMSO, acetone and ethanol), at concentrations determined to have no significant effect on measured endpoints. On the one hand, regeneration was significantly inhibited at (nominal) concentrations of 1, 5 and 1 mg/L for gemfibrozil, ibuprofen and naproxen respectively and at the higher concentration of 50 mg/L for bezafibrate and trimethoprim. On the other hand, carbamazepine and the antibiotics sulfapyridine, oxytetracycline and novobiocin significantly increased regeneration at 25, 5, 50 and 50 mg/L respectively. Relatively high IC50 values of 0.9, 3.84, 4.9 and 22.5 mg/L were calculated for gemfibrozil, ibuprofen, naproxen and bezafibrate, respectively. However when subjected to tier two toxicity assessment under EU regulatory guidance using environmentally relevant concentrations a MEC/PNEC value>1 was calculated for gemfibrozil, ibuprofen and naproxen indicating teratogenic potential and the necessity for further tier three assessment. A toxicity index (TI) was also calculated using three different techniques, with TI values>3 (indicating teratogenic potential) found for gemfibrozil, ibuprofen, naproxen and bezafibrate and >1 (indicating a weak teratogenic potential) found for carbamazepine. These results are discussed in the context of their environmental relevance and toxic potential.
- Published
- 2008
- Full Text
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32. An investigation into the acute and chronic toxicity of eleven pharmaceuticals (and their solvents) found in wastewater effluent on the cnidarian, Hydra attenuata.
- Author
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Quinn B, Gagné F, and Blaise C
- Subjects
- Animals, Lethal Dose 50, Solvents chemistry, Toxicity Tests, Acute, Toxicity Tests, Chronic, Water Pollutants, Chemical chemistry, Environmental Monitoring methods, Hydra drug effects, Pharmaceutical Preparations chemistry, Solvents toxicity, Water Pollutants, Chemical toxicity
- Abstract
Pharmaceuticals previously identified in the effluent from the wastewater treatment plant (WWTP) in Montreal discharging into the St. Lawrence river, were tested for acute and chronic toxicity using the cnidarian Hydra attenuata. Acute toxicity was based on the established technique looking at morphological changes in the Hydra, while recently developed endpoints of feeding behaviour, attachment and growth (hydranth number) were used to measure chronic effects. The compounds under investigation (ibuprofen, naproxen, gemfibrozil, bezafibrate, carbamazepine, sulfamethoxazole, sulfapyridine, oxytetracycline, novobiocin, trimethoprim and caffeine) were tested individually in controlled laboratory exposures with LC(50) and EC(50) results calculated. All compounds tested had relatively high LC(50) values with gemfibrozil, ibuprofen and naproxen having the lowest at 22.36 mg/L and EC(50) values based on morphology of 1.18 to 2.62 mg/L (all concentrations are nominal). The EC(50) values based on feeding were similar to those based on morphology but with increased sensitivity for carbamazepine, bezafibrate and novobiocin. A trend of a reduction in feeding with deterioration in morphology was observed in the Hydra, with the exception of novobiocin, where a lower than expected EC(50) of 13.53 mg/L was found with no negative effect on morphology. Significant reductions in attachment and hydranth number were seen at concentrations of 1 and 5 mg/L for gemfibrozil and ibuprofen respectively. A toxicity threshold (TT) of 320 microg/L was calculated for ibuprofen, only a factor of 10(2) or 10 higher than the concentration found in the effluent in the present study (1.19 mug/L) and in other Canadian effluents studied (22 microg/L [Brun GL, Bernier M, Losier R, Doe K, Jackman P, Lee HB, Pharmaceutically active compounds in Atlantic Canadian sewage treatment plant effluents and receiving waters and potential for environmental effects as measured by acute and chronic aquatic toxicity. Environ Toxicol Chem 2006; 25(8): 2163-2176.] respectively. Using EU directive 93/67/EEC the pharmaceuticals under investigation can be classified as toxic (gemfibrozil, ibuprofen and naproxen), harmful (carbamazepine, bezafibrate, sulfapyridine, oxytetracycline and novobiocin) and non-toxic (sulfamethoxazole, trimethoprim and caffeine) and their potential toxicity for the aquatic environment is discussed.
- Published
- 2008
- Full Text
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33. Identification of compounds from Etonia rosemary (Conradina etonia).
- Author
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Quinn BP, Bernier UR, and Booth MM
- Subjects
- Gas Chromatography-Mass Spectrometry, Plant Extracts chemistry, Volatilization, Organic Chemicals analysis, Rosmarinus chemistry
- Abstract
Mosquitoes transmit pathogens that result in diseases harmful to human, livestock, and wildlife hosts. Numerous measures can be used to reduce insect-borne disease risk to humans, and one approach is the use of topical repellents to prevent host-seeking arthropods from taking a blood meal. A current emphasis in the development of new repellents is that they be safe. Therefore, natural products sources are increasingly being explored. Compounds from plants of the mint family (Lamiaceae) have been demonstrated to be insect repellents. This study examines compounds from Etonia rosemary (Conradina etonia) to identify compounds for examination as insect repellents. Samples of Etonia rosemary were passively extracted with hexane, dichloromethane, and methanol and analyzed by GC/MS. This extraction method was chosen to eliminate thermal degradation of plant components that can occur during the distillation procedure. Additional headspace volatile compounds from this plant were identified using microscale purge-and-trap GC/MS. A variety of terpenes, terpenic alcohols, ketones, and aldehydes were identified in the extracts with terpenes and short-chained aldehydes detected in greatest abundance.
- Published
- 2007
- Full Text
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34. Analysis of extracted and volatile components in blackstrap molasses feed as candidate house fly attractants.
- Author
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Quinn BP, Bernier UR, Geden CJ, Hogsette JA, and Carlson DA
- Subjects
- Animals, Houseflies drug effects, Insect Control, Oils, Volatile pharmacology, Pheromones pharmacology, Molasses analysis, Oils, Volatile analysis, Pest Control, Biological, Pheromones analysis
- Abstract
House flies are a ubiquitous insect that have the potential to spread many diseases to humans and livestock. Managing house fly populations is accomplished by having desirable baits, traps, and killing agents. Most house fly baits are designed for outdoor use or limited indoor use, and have a foul odor that is not conducive to food preparatory and dining areas. Blackstrap molasses has long been used as a house fly bait, but it is sticky and viscous, making it difficult to handle. This study sought to identify compounds present in blackstrap molasses that might be attractive to house flies, and therefore, provide the public with an indoor bait that does not have an offensive smell and is easy to handle. Indoor bioassays with house flies using 50% blackstrap molasses diluted in deionized water, a hexane extract of blackstrap molasses, and deionized water, elicited 86.2%, 70.6%, and 13.8% responses, respectively. Hexane and diethyl ether extracts of blackstrap molasses produced a large number of compounds with widely differing organic structures including substituted phenols, nitrogen and oxygen heterocycles, carboxylic acids, and many other organic compounds.
- Published
- 2007
- Full Text
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35. Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model.
- Author
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Sun Y, Quinn B, Xu YH, Leonova T, Witte DP, and Grabowski GA
- Subjects
- Animals, Brain pathology, Doxycycline pharmacology, Female, Glucosylceramidase biosynthesis, Humans, Lipids analysis, Liver pathology, Lung pathology, Male, Mice, Point Mutation, Spleen pathology, Viscera metabolism, Disease Models, Animal, Gaucher Disease enzymology, Gaucher Disease pathology, Gene Expression, Glucosylceramidase genetics, Glucosylceramidase metabolism, Viscera pathology
- Abstract
The reversibility and regression of histological and biochemical findings in a mouse model of Gaucher disease (4L/PS-NA) was evaluated using a liver-enriched activator protein promoter control of a tetracycline-controlled transcriptional activation-responsive human acid beta-glucosidase (hGCase) transgenic system. 4L/PS-NA has the acid beta-glucosidase (GCase) V394L/V394L (4L) point mutation combined with hypomorphic ( approximately 6% wild-type) expression of the mouse prosaposin transgene (PS-NA). The hGCase/4L/PS-NA had exclusive liver expression of hGCase controlled by doxycycline (DOX). In the absence of DOX, hGCase was secreted from liver at levels of approximately 120 microg/ml serum with only approximately 8% of full activity, following exposure to pH 7.4 in serum. The hGCase activity and protein were detected in cells of the liver (massive), lung, and spleen, but not the brain. The visceral tissue storage cells and glucosylceramide (GC) accumulation in hGCase/4L/PS-NA were decreased from that in 4L/PS-NA mice. Turning off hGCase expression with dietary DOX led to reaccumulation of storage cells and of GC in liver, lung, and spleen, and macrophage activation in those tissues. This study demonstrates that conditionally expressed hGCase supplemented the existing mutant mouse GCase to control visceral substrate accumulation in vivo.
- Published
- 2006
- Full Text
- View/download PDF
36. Gaucher disease mouse models: point mutations at the acid beta-glucosidase locus combined with low-level prosaposin expression lead to disease variants.
- Author
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Sun Y, Quinn B, Witte DP, and Grabowski GA
- Subjects
- Animals, Brain metabolism, Brain pathology, Crosses, Genetic, Glucosylceramidase biosynthesis, Glucosylceramides analysis, Liver pathology, Lung pathology, Mice, Phenotype, Point Mutation, Spleen pathology, Thymus Gland pathology, Transgenes, Disease Models, Animal, Gaucher Disease genetics, Glucosylceramidase deficiency, Glucosylceramidase genetics, Saposins biosynthesis
- Abstract
Gaucher disease is a common lysosomal storage disease caused by a defect of acid beta-glucosidase (GCase). The optimal in vitro hydrolase activity of GCase requires saposin C, an activator protein that derives from a precursor, prosaposin. To develop additional models of Gaucher disease and to test in vivo effects of saposin deficiencies, mice expressing low levels (4--45% of wild type) of prosaposin and saposins (PS-NA) were backcrossed into mice with specific point mutations (V394L/V394L or D409H/D409H) of GCase. The resultant mice were designated 4L/PS-NA and 9H/PS-NA, respectively. In contrast to PS-NA mice, the 4L/PS-NA and 9H/PS-NA mice displayed large numbers of engorged macrophages and nearly exclusive glucosylceramide (GC) accumulation in the liver, lung, spleen, thymus, and brain. Electron microscopy of the storage cells showed the characteristic tubular storage material of Gaucher cells. Compared with V394L/V394L mice, 4L/PS-NA mice that expressed 4--6% of wild-type prosaposin levels had approximately 25--75% decreases in GCase activity and protein in liver, spleen, and fibroblasts. These results imply that reduced saposin levels increased the instability of V394L or D409H GCases and that these additional decreases led to large accumulations of GC in all tissues. These models mimic a more severe Gaucher disease phenotype and could be useful for therapeutic intervention studies.
- Published
- 2005
- Full Text
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37. Effects of age on volumes of cortex, white matter and subcortical structures.
- Author
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Walhovd KB, Fjell AM, Reinvang I, Lundervold A, Dale AM, Eilertsen DE, Quinn BT, Salat D, Makris N, and Fischl B
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Aging physiology, Brain Mapping, Cerebral Cortex physiology, Female, Functional Laterality physiology, Humans, Image Processing, Computer-Assisted methods, Lateral Ventricles, Magnetic Resonance Imaging methods, Male, Middle Aged, Neural Pathways, Regression Analysis, Statistics, Nonparametric, Aging pathology, Cerebral Cortex pathology
- Abstract
The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.
- Published
- 2005
- Full Text
- View/download PDF
38. Ecotoxicological effects of a semi-submerged municipal dump (Castle harbour, Bermuda) on the Calico scallop Argopecten gibbus.
- Author
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Quinn B, Gagné F, Weber JP, and Blaise C
- Subjects
- Analysis of Variance, Animals, Bermuda, Biomarkers analysis, DNA Damage genetics, Gills drug effects, Gills metabolism, Glutathione Transferase metabolism, Lipid Peroxidation drug effects, Metallothionein metabolism, Metals, Heavy analysis, Metals, Heavy toxicity, Pectinidae chemistry, Vitellins metabolism, Environmental Exposure, Environmental Monitoring statistics & numerical data, Pectinidae drug effects, Refuse Disposal, Water Pollutants, Chemical toxicity
- Abstract
A biomarker study was undertaken using the Calico scallop Argopecten gibbus to assess the ecotoxicological effects of a semi-submerged municipal dump on the adjacent patch reef lagoon ecosystem (Castle harbour, Bermuda). Caged scallops were deployed in situ for 2 months at various distances from the dump (50 m, 900 m and 2.7 km) and at a reference site (14 km). A suite of biomarkers comprising metallothionein (MT), lipid peroxidation (LPO), vitellin-like proteins (Vn), glutathione S-transferase (GST), DNA strand breaks and condition factor (CF) were investigated in various tissues of the scallop (gill, digestive gland and gonad). Levels of heavy metals were also measured in the whole scallop soft tissue. While there was some variation in response between tissues, in general the results indicated that the dump was negatively impacting scallops deployed in the adjacent marine environment: elevated levels of MT, DNA strand breaks, Vn and GST and reduced condition factor were found for scallops deployed nearest to the dump and at the site 1.5 km from this point source of contamination (Tuckers town) in Castle harbour, with respect to the reference site, North Rock (although this exhibited some degree of metal contamination). The gills from scallops deployed at the dump site were the most responsive tissue, with the highest expression of MT, LPO and DNA damage. This study indicates the potential of the Calico scallop as a convenient bioindicator species in the marine tropical benthos.
- Published
- 2005
- Full Text
- View/download PDF
39. Viable mouse models of acid beta-glucosidase deficiency: the defect in Gaucher disease.
- Author
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Xu YH, Quinn B, Witte D, and Grabowski GA
- Subjects
- Animals, Blotting, Northern, Gaucher Disease pathology, Genotype, Glucosylceramidase metabolism, Glycosphingolipids analysis, Mice, Phenotype, Point Mutation, Polymerase Chain Reaction, Disease Models, Animal, Gaucher Disease genetics, Glucosylceramidase deficiency, Glucosylceramidase genetics
- Abstract
Gaucher disease is an autosomal recessively inherited disease caused by mutations at the acid beta-glucosidase (GCase) locus (GBA). To develop viable models of Gaucher disease, point mutations (pmuts), encoding N370S, V394L, D409H, or D409V were introduced into the mouse GCase (gba) locus. DNA sequencing verified each unique pmut. Mutant GCase mRNAs were near wild-type (WT) levels. GCase activities were reduced to 2 to 25% of WT in liver, lung, spleen, and cultured fibroblasts from pmut/pmut or pmut/null mice. The corresponding brain GCase activities were approximately 25% of WT. N370S homozygosity was lethal in the neonatal period. For the other pmut mice, a few storage cells appeared in the spleen at > or =7 months (D409H or D409V homozygotes) or > or =1 year (V394L homozygotes). V394L/null, D409H/null, or D409V/null mice showed scattered storage cells in spleen at approximately 3 to 4 months. Occasional storage cells (sinusoidal cells) were present in liver. In D409V/null mice, large numbers of Mac-3-positive storage cells (ie, macrophages) accumulated in the lung. Glycosphingolipid analyses showed varying rates of progressive glucosylceramide accumulation in visceral organs of pmut/pmut or pmut/null mice, but not in brain. These GCase-deficient mice provide tools for gaining insight into the pathophysiology of Gaucher disease and developing improved therapies.
- Published
- 2003
- Full Text
- View/download PDF
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