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2. Dementias Platform UK: Bringing genetics into life.

Author

Leonenko, Ganna, Bauermeister, Sarah, Ghanti, Dipanwita, Stevenson‐Hoare, Joshua, Simmonds, Emily, Brookes, Keeley, Morgan, Kevin, Chaturvedi, Nishi, Elliott, Paul, Thomas, Alan, Wareham, Nicholas, Gallacher, John, and Escott‐Price, Valentina

Abstract

INTRODUCTION: The Dementias Platform UK (DPUK) Data Portal is a data repository bringing together a wide range of cohorts. Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and an overlapping genetic component that is poorly understood. The DPUK collection of independent cohorts can facilitate research in neurodegeneration by combining their genetic and phenotypic data. METHODS: For genetic data processing, pipelines were generated to perform quality control analysis, genetic imputation, and polygenic risk score (PRS) derivation with six genome‐wide association studies of neurodegenerative diseases. Pipelines were applied to five cohorts. DISCUSSION: The data processing pipelines, research‐ready imputed genetic data, and PRS scores are now available on the DPUK platform and can be accessed upon request though the DPUK application process. Harmonizing genome‐wide data for multiple datasets increases scientific opportunity and allows the wider research community to access and process data at scale and pace. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Improving Representation of Women in the Chemical Engineering Undergraduate Curriculum

Author

Morgan, Kevin

Abstract

The United Nations has set Sustainable Development Goals (SDGs) for Quality Education and Gender Equality, both of which have impact in education, including Science, Technology, Engineering, and Mathematics (STEM) Education, which includes Chemistry and Chemical Engineering. To achieve these aspirations, some habitual obstacles must be overcome, not least the lack of inclusive representation of women in STEM teaching resources, an issue for all levels of the Education sector, including Higher Education. A recent opportunity to teach catalysis and catalytic reactors, a topic in which the author has substantial background, combined with a desire to contribute to the success of the SDGs provided the platform to address some of the historical gender bias in teaching resources, albeit in only a small way. At the start of the delivery of a 20 h block of teaching over a 6-week period, historical and contemporary women were discussed as part of important contributions to catalysis and catalytic reactors in the chemical industries. The highlighting of women in engineering resonated with some of the students, and this was reflected in the evaluations provided at the end of the content. This prompted a more targeted evaluation of the intervention of showcasing women in engineering, which reported a positive impact on participating students. The results of that follow-up evaluation highlighted that gender balance in role models was important to students, and the intervention was received positively.

Published
2024
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5. Evaluating the Impact of Project-Based Learning in Supporting Students with the A-Level Chemistry Curriculum in Northern Ireland

Author

McLaughlin, Shannon, Amir, Haris, Garrido, Neil, Turnbull, Clare, Rouncefield-Swales, Alison, Swadźba-Kwaśny, Malgorzata, and Morgan, Kevin

Abstract

Toward Greener Fragrances (TGF) is a collaboration between the Institute for Research in Schools (IRIS) and the Ionic Liquids Laboratory (QUILL) at Queen’s University Belfast (QUB) supported by funding from the Royal Society of Chemistry (RSC). TGF provided forty-nine post-16 students with a different perspective on chemistry, allowing them to experience the creativity of scientific research and learn how it relates to the real world. The project created the opportunity to work in an emerging scientific field that is accessible to students who, it transpired, have a real passion for higher-level chemistry. During the course of the eight-month extra-curricular project, students gained hands-on research experience in risk assessment, design of experiments, lab-based synthesis, and analysis, all of which was facilitated either in their respective schools or at university research facilities. The climax of the project was the opportunity for students to participate in a research conference. Hence, the project allowed them to work on chemical reactions studied at the A-level, develop practical skills, and gain insight into the research profession. Participants were surveyed at registration and at the end of their involvement to assess the impact of the project on the knowledge of chemistry and career aspirations. Teachers observed that the project encouraged students to work collaboratively, an experience that the students themselves reported as enjoyable. It is clear that the project had a significant positive impact on those who participated.

Published
2024
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7. A DNA Algorithm for Calculating the Maximum Flow of a Network

Author

Sackmann, Andrea, Brown, Kristelle, Formanowicz, Piotr, Morgan, Kevin, Kalsheker, Noor, Garibaldi, Jon M., and Błażewicz, Jacek

Abstract

DNA computing is a highly interdisciplinary field which combines molecular operations with theoretical algorithm design. A number of algorithms have been demonstrated in DNA computing, but to date network flow problems have not been studied. We aim to provide an approach to calculate the value of the maximum flow in networks by encoding the mathematical problem in DNA molecules and by using molecular biology techniques to manipulate the DNA. We present results which demonstrate that the algorithm works for an example network problem.

Published
2023
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8. BOOK REVIEWS

Author

CHRISTENSEN, JOSEPH, CURTHOYS, ANN, FRANCES, RAELENE, MCCALMAN, JANET, MELLEUISH, GREG, MORGAN, KEVIN, OLIVER, BOBBIE, REID, ROB, RISEMAN, NOAH, STEPHENS, DAVID, and WRIGHT, CLAIRE E. F.

Published
2023
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10. Delivering micro-missions in public food transitions: Harnessing tensions for creative outcomes.

Author

Henderson, Dylan, Morgan, Kevin, and Delbridge, Rick

Abstract

• We examine tensions and contestation amongst actors in the delivery of place-based micro-missions. • The rationale, goals, implementation and evaluation of micro-missions are shown to be characterised by contestation which challenges the achievement of mission outputs and outcomes. • We outline how place-based actors may be able to negotiate these tensions within the context of a micro-mission to produce creative responses in learning and action. • Three mechanisms are identified to produce creative responses to tensions, including proactive governance, distributed leadership and place-based experimentation. Micro-missions represent small-scale, place-based strategies for societal innovation, distinct from grand missions that target national-level transformations. They offer potential for collaborative engagement among local stakeholders in the public sector, businesses, and civil society that aims to address local needs and promote wider innovation, particularly for social and ecological progress. Despite the potential for place-based micro-missions to provide a more focused approach to tackling societal challenges, the practicalities of delivering such a strategy remain uncertain. Through an exploration of a Welsh (UK) public food micro-mission, we identify the evolving tensions and conflicts and their impact on such micro-missions and their outcomes. Our findings underscore the potential significance of tensions throughout the micro-mission process. They highlight the crucial role of regional actors in generating creative responses to tensions through proactive governance, distributed leadership, and place-based experimentation. [ABSTRACT FROM AUTHOR]

Published
2024
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12. New insights into the genetic etiology of Alzheimer’s disease and related dementias

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris E., Kleineidam, Luca, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C., Campos-Martin, Rafael, Grenier-Boley, Benjamin, Andrade, Victor, Holmans, Peter A., Boland, Anne, Damotte, Vincent, van der Lee, Sven J., Costa, Marcos R., Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C., Yaqub, Amber, Prokic, Ivana, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Aarsland, Dag, Garcia-Gonzalez, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alcolea, Daniel, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J., Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Barral, Sandra, Beiser, Alexa, Pastor, Ana Belén, Below, Jennifer E., Benchek, Penelope, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizarro, Alessandra, Blesa, Rafael, Boada, Mercè, Boerwinkle, Eric, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bressler, Jan, Bresner, Catherine, Brodaty, Henry, Brookes, Keeley J., Brusco, Luis Ignacio, Buiza-Rueda, Dolores, Bûrger, Katharina, Burholt, Vanessa, Bush, William S., Calero, Miguel, Cantwell, Laura B., Chene, Geneviève, Chung, Jaeyoon, Cuccaro, Michael L., Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chen, Hung-Hsin, Chillotti, Caterina, Ciccone, Simona, Claassen, Jurgen A. H. R., Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D., Debette, Stéphanie, Deckert, Jürgen, del Ser, Teodoro, Denning, Nicola, DeStefano, Anita, Dichgans, Martin, Diehl-Schmid, Janine, Diez-Fairen, Mónica, Rossi, Paolo Dionigi, Djurovic, Srdjan, Duron, Emmanuelle, Düzel, Emrah, Dufouil, Carole, Eiriksdottir, Gudny, Engelborghs, Sebastiaan, Escott-Price, Valentina, Espinosa, Ana, Ewers, Michael, Faber, Kelley M., Fabrizio, Tagliavini, Nielsen, Sune Fallgaard, Fardo, David W., Farotti, Lucia, Fenoglio, Chiara, Fernández-Fuertes, Marta, Ferrari, Raffaele, Ferreira, Catarina B., Ferri, Evelyn, Fin, Bertrand, Fischer, Peter, Fladby, Tormod, Fließbach, Klaus, Fongang, Bernard, Fornage, Myriam, Fortea, Juan, Foroud, Tatiana M., Fostinelli, Silvia, Fox, Nick C., Franco-Macías, Emlio, Bullido, María J., Frank-García, Ana, Froelich, Lutz, Fulton-Howard, Brian, Galimberti, Daniela, García-Alberca, Jose Maria, García-González, Pablo, Garcia-Madrona, Sebastian, Garcia-Ribas, Guillermo, Ghidoni, Roberta, Giegling, Ina, Giorgio, Giaccone, Goate, Alison M., Goldhardt, Oliver, Gomez-Fonseca, Duber, González-Pérez, Antonio, Graff, Caroline, Grande, Giulia, Green, Emma, Grimmer, Timo, Grünblatt, Edna, Grunin, Michelle, Gudnason, Vilmundur, Guetta-Baranes, Tamar, Haapasalo, Annakaisa, Hadjigeorgiou, Georgios, Haines, Jonathan L., Hamilton-Nelson, Kara L., Hampel, Harald, Hanon, Olivier, Hardy, John, Hartmann, Annette M., Hausner, Lucrezia, Harwood, Janet, Heilmann-Heimbach, Stefanie, Helisalmi, Seppo, Heneka, Michael T., Hernández, Isabel, Herrmann, Martin J., Hoffmann, Per, Holmes, Clive, Holstege, Henne, Vilas, Raquel Huerto, Hulsman, Marc, Humphrey, Jack, Biessels, Geert Jan, Jian, Xueqiu, Johansson, Charlotte, Jun, Gyungah R., Kastumata, Yuriko, Kauwe, John, Kehoe, Patrick G., Kilander, Lena, Ståhlbom, Anne Kinhult, Kivipelto, Miia, Koivisto, Anne, Kornhuber, Johannes, Kosmidis, Mary H., Kukull, Walter A., Kuksa, Pavel P., Kunkle, Brian W., Kuzma, Amanda B., Lage, Carmen, Laukka, Erika J., Launer, Lenore, Lauria, Alessandra, Lee, Chien-Yueh, Lehtisalo, Jenni, Lerch, Ondrej, Lleó, Alberto, Longstreth, William, Lopez, Oscar, de Munain, Adolfo Lopez, Love, Seth, Löwemark, Malin, Luckcuck, Lauren, Lunetta, Kathryn L., Ma, Yiyi, Macías, Juan, MacLeod, Catherine A., Maier, Wolfgang, Mangialasche, Francesca, Spallazzi, Marco, Marquié, Marta, Marshall, Rachel, Martin, Eden R., Montes, Angel Martín, Rodríguez, Carmen Martínez, Masullo, Carlo, Mayeux, Richard, Mead, Simon, Mecocci, Patrizia, Medina, Miguel, Meggy, Alun, Mehrabian, Shima, Mendoza, Silvia, Menéndez-González, Manuel, Mir, Pablo, Moebus, Susanne, Mol, Merel, Molina-Porcel, Laura, Montrreal, Laura, Morelli, Laura, Moreno, Fermin, Morgan, Kevin, Mosley, Thomas, Nöthen, Markus M., Muchnik, Carolina, Mukherjee, Shubhabrata, Nacmias, Benedetta, Ngandu, Tiia, Nicolas, Gael, Nordestgaard, Børge G., Olaso, Robert, Orellana, Adelina, Orsini, Michela, Ortega, Gemma, Padovani, Alessandro, Paolo, Caffarra, Papenberg, Goran, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Peloso, Gina, Pérez-Cordón, Alba, Pérez-Tur, Jordi, Pericard, Pierre, Peters, Oliver, Pijnenburg, Yolande A. L., Pineda, Juan A., Piñol-Ripoll, Gerard, Pisanu, Claudia, Polak, Thomas, Popp, Julius, Posthuma, Danielle, Priller, Josef, Puerta, Raquel, Quenez, Olivier, Quintela, Inés, Thomassen, Jesper Qvist, Rábano, Alberto, Rainero, Innocenzo, Rajabli, Farid, Ramakers, Inez, Real, Luis M., Reinders, Marcel J. T., Reitz, Christiane, Reyes-Dumeyer, Dolly, Ridge, Perry, Riedel-Heller, Steffi, Riederer, Peter, Roberto, Natalia, Rodriguez-Rodriguez, Eloy, Rongve, Arvid, Allende, Irene Rosas, Rosende-Roca, Maitée, Royo, Jose Luis, Rubino, Elisa, Rujescu, Dan, Sáez, María Eugenia, Sakka, Paraskevi, Saltvedt, Ingvild, Sanabria, Ángela, Sánchez-Arjona, María Bernal, Sanchez-Garcia, Florentino, Juan, Pascual Sánchez, Sánchez-Valle, Raquel, Sando, Sigrid B., Sarnowski, Chloé, Satizabal, Claudia L., Scamosci, Michela, Scarmeas, Nikolaos, Scarpini, Elio, Scheltens, Philip, Scherbaum, Norbert, Scherer, Martin, Schmid, Matthias, Schneider, Anja, Schott, Jonathan M., Selbæk, Geir, Seripa, Davide, Serrano, Manuel, Sha, Jin, Shadrin, Alexey A., Skrobot, Olivia, Slifer, Susan, Snijders, Gijsje J. L., Soininen, Hilkka, Solfrizzi, Vincenzo, Solomon, Alina, Song, Yeunjoo, Sorbi, Sandro, Sotolongo-Grau, Oscar, Spalletta, Gianfranco, Spottke, Annika, Squassina, Alessio, Stordal, Eystein, Tartan, Juan Pablo, Tárraga, Lluís, Tesí, Niccolo, Thalamuthu, Anbupalam, Thomas, Tegos, Tosto, Giuseppe, Traykov, Latchezar, Tremolizzo, Lucio, Tybjærg-Hansen, Anne, Uitterlinden, Andre, Ullgren, Abbe, Ulstein, Ingun, Valero, Sergi, Valladares, Otto, Broeckhoven, Christine Van, Vance, Jeffery, Vardarajan, Badri N., van der Lugt, Aad, Dongen, Jasper Van, van Rooij, Jeroen, van Swieten, John, Vandenberghe, Rik, Verhey, Frans, Vidal, Jean-Sébastien, Vogelgsang, Jonathan, Vyhnalek, Martin, Wagner, Michael, Wallon, David, Wang, Li-San, Wang, Ruiqi, Weinhold, Leonie, Wiltfang, Jens, Windle, Gill, Woods, Bob, Yannakoulia, Mary, Zare, Habil, Zhao, Yi, Zhang, Xiaoling, Zhu, Congcong, Zulaica, Miren, Farrer, Lindsay A., Psaty, Bruce M., Ghanbari, Mohsen, Raj, Towfique, Sachdev, Perminder, Mather, Karen, Jessen, Frank, Ikram, M. Arfan, de Mendonça, Alexandre, Hort, Jakub, Tsolaki, Magda, Pericak-Vance, Margaret A., Amouyel, Philippe, Williams, Julie, Frikke-Schmidt, Ruth, Clarimon, Jordi, Deleuze, Jean-François, Rossi, Giacomina, Seshadri, Sudha, Andreassen, Ole A., Ingelsson, Martin, Hiltunen, Mikko, Sleegers, Kristel, Schellenberg, Gerard D., van Duijn, Cornelia M., Sims, Rebecca, van der Flier, Wiesje M., Ruiz, Agustín, Ramirez, Alfredo, and Lambert, Jean-Charles

Abstract

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOEε4 allele.

Published
2022
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13. Targeted bisulfite sequencing analysis of Alzheimer's disease candidate genes reveals differential methylation across neurofibrillary tangle burden in the prefrontal cortex.

Author

Wheildon, Greg, Smith, Adam R., Soanes, Darren, Smith, Rebecca G., Moore, Karen, O'Neill, Paul, Morgan, Kevin, Thomas, Alan J, Love, Seth, Francis, Paul T, Mill, Jonathan, Pishva, Ehsan, and Lunnon, Katie

Abstract

Background: Recent epigenome‐wide association studies (EWAS) identified several loci in specific genes showing robust and reproducible alterations in DNA methylation in Alzheimer's disease (AD) brain samples. Standardly, assessing methylation in EWAS is done using microarrays, which target a limited number of sites in each gene. Here, we performed targeted bisulfite sequencing of candidate genes associated with AD to determine the exact extent of methylation changes across neurofibrillary tangle burden (NFT) within these loci. Method: Prefrontal cortex brain samples from 58 individuals were grouped by Braak stage (control 0‐II; intermediate III‐IV; AD V‐VI). Following DNA extraction, 30 genomic regions were captured using Agilent SureSelect target baits. After next‐generation bisulfite sequencing, reads were aligned and the methylation status of cytosine residues called using the Bismark program. Differentially methylated positions (DMPs) were analyzed across the three groups. Furthermore, the presence of differentially methylated regions (DMRs), made up of several DMPs was assessed. Methylation levels in genomic features, such as promoters and gene bodies, of the target regions were also compared. Result: Methylation levels were quantified for each group. Linear regression controlled for co‐variation before differences were examined using a one‐way ANOVA, with Tukey's post‐hoc test. Sites in several genes showed stepwise increases in DNA methylation across the groups. Interestingly, amongst the most robust sites, differences in methylation in the intermediate group when compared to the control and AD samples were observed. DMRs were observed in the groups, as were methylation differences between promotors and gene bodies in several targeted regions. Conclusion: This work provides further evidence that dysregulation of methylation is associated with pathological changes in AD prefrontal cortex. Differential methylation with intermediate NFT pathology, at sites showing no difference between control and AD samples, potentially indicates early pathological changes. As DNA methylation is reversible, this could present potential targets for pharmacological intervention. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Targeted bisulfite sequencing analysis of Alzheimer's disease candidate genes reveals differential methylation across neurofibrillary tangle burden in the prefrontal cortex.

Author

Wheildon, Greg, Smith, Adam R., Soanes, Darren, Smith, Rebecca G., Moore, Karen, O'Neill, Paul, Morgan, Kevin, Thomas, Alan J, Love, Seth, Francis, Paul T, Mill, Jonathan, Pishva, Ehsan, and Lunnon, Katie

Abstract

Background: Recent epigenome‐wide association studies (EWAS) identified several loci in specific genes showing robust and reproducible alterations in DNA methylation in Alzheimer's disease (AD) brain samples. Standardly, assessing methylation in EWAS is done using microarrays, which target a limited number of sites in each gene. Here, we performed targeted bisulfite sequencing of candidate genes associated with AD to determine the exact extent of methylation changes across neurofibrillary tangle burden (NFT) within these loci. Method: Prefrontal cortex brain samples from 58 individuals were grouped by Braak stage (control 0‐II; intermediate III‐IV; AD V‐VI). Following DNA extraction, 30 genomic regions were captured using Agilent SureSelect target baits. After next‐generation bisulfite sequencing, reads were aligned and the methylation status of cytosine residues called using the Bismark program. Differentially methylated positions (DMPs) were analyzed across the three groups. Furthermore, the presence of differentially methylated regions (DMRs), made up of several DMPs was assessed. Methylation levels in genomic features, such as promoters and gene bodies, of the target regions were also compared. Result: Methylation levels were quantified for each group. Linear regression controlled for co‐variation before differences were examined using a one‐way ANOVA, with Tukey's post‐hoc test. Sites in several genes showed stepwise increases in DNA methylation across the groups. Interestingly, amongst the most robust sites, differences in methylation in the intermediate group when compared to the control and AD samples were observed. DMRs were observed in the groups, as were methylation differences between promotors and gene bodies in several targeted regions. Conclusion: This work provides further evidence that dysregulation of methylation is associated with pathological changes in AD prefrontal cortex. Differential methylation with intermediate NFT pathology, at sites showing no difference between control and AD samples, potentially indicates early pathological changes. As DNA methylation is reversible, this could present potential targets for pharmacological intervention. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Exome sequencing identifies rare damaging variants in ATP8B4and ABCA1as risk factors for Alzheimer’s disease

Author

Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen G. J., Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J., Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W., Berr, Claudine, Bis, Joshua C., Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J. Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L., Farrer, Lindsay A., Fernández, Maria Victoria, Fox, Nick C., Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan J. P., Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L., Holmes, Clive, Ikram, M. Arfan, Ikram, M. Kamran, Jansen, Iris E., Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W., Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel M. A. M., Marshall, Rachel, Martin, Eden R., Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O., Morgan, Kevin, Myers, Richard M., Nacmias, Benedetta, Naj, Adam C., Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A., Raybould, Rachel, Redon, Richard, Reinders, Marcel J. T., Richard, Anne-Claire, Riedel-Heller, Steffi G., Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S., Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D., Scheltens, Philip, Schott, Jonathan M., Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A., Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G., van der Lee, Sven J., Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C., Greicius, Michael D., Yokoyama, Jennifer S., Cruchaga, Carlos, Hardy, John, Ramirez, Alfredo, Mead, Simon, van der Flier, Wiesje M., van Duijn, Cornelia M., Williams, Julie, Nicolas, Gaël, Bellenguez, Céline, and Lambert, Jean-Charles

Abstract

Alzheimer’s disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals—16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4and ABCA1with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1and ACEhighlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.

Published
2022
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16. RPS16 and NOL6 splice region variants are associated with early onset Alzheimer's disease: Basic science and pathogenesis: Genetics and omics of AD.

Author

Guen, Yann Le, Napolioni, Valerio, Belloy, Michael E., Eger, Sarah J., Kennedy, Gabriel, Morgan, Kevin, and Greicius, Michael D.

Abstract

Background: Common genetic polymorphisms identified by genome wide association explain less than half the genetic variance of Alzheimer's disease (AD). Rare genetic mutations with larger effect sizes than common variants are expected to contribute to this missing heritability. We developed an extreme phenotype filtering‐based approach to identify rare candidate causal variants. Method: Figure 1 describes our analysis pipeline. Briefly, we removed AD cases who had a discordant pathology diagnosis, or a known pathogenic mutation, and duplicated individuals (using identity‐by‐descent). We then restricted the analysis to APOE4‐negative cases with age‐at‐onset below 70 and required controls to be cognitively normal over 75. We started with variants present in ADSP whole exome sequencing data to guarantee a minimum number of control subjects for filtering. We restricted our analysis to variants with impact equal to high, moderate, or modifier annotated by Ensembl Variant Effect Predictor. We removed any variants seen in controls over 75 and in less than four early‐onset cases (heuristic threshold). For this case‐filtering step, we limited variant‐count contribution from ADSP extension to two cases because this cohort contains early‐onset pedigrees. We determined the carriers' ancestral background using SNPWeight and prioritized variants seen in multiple ancestries (assuming that variants increasing AD risk across ancestries are more likely to be causal). UK Biobank was used as a replication cohort for remaining variants (provided that their calls in subjects with both WES data and SNP‐array imputed data demonstrated sufficiently accurate imputation metrics). Variants association with AD diagnosis and AD in siblings was tested, covarying by sex, APOE2 and APOE4 dosages, and the first 10 genetic principal components accounting for population structure. Genes harboring identified variants were tested for differential expression between cases and controls. Result: Our pipeline identified two variants (Table 1). Table 2 presents the carriers demographics. Table 3 shows the imputation quality and association results in the UK Biobank. Figure 2 emphasizes that NOL6 is upregulated in AD compare to controls across brain regions, while Figure 3 underlines that RPS16 is downregulated. Conclusion: NOL6 splice region and RPS16 splice donor variants may increase AD risk and should be tested in additional cohorts. [ABSTRACT FROM AUTHOR]

Published
2020
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17. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Author

Chia, Ruth, Sabir, Marya S., Bandres-Ciga, Sara, Saez-Atienzar, Sara, Reynolds, Regina H., Gustavsson, Emil, Walton, Ronald L., Ahmed, Sarah, Viollet, Coralie, Ding, Jinhui, Makarious, Mary B., Diez-Fairen, Monica, Portley, Makayla K., Shah, Zalak, Abramzon, Yevgeniya, Hernandez, Dena G., Blauwendraat, Cornelis, Stone, David J., Eicher, John, Parkkinen, Laura, Ansorge, Olaf, Clark, Lorraine, Honig, Lawrence S., Marder, Karen, Lemstra, Afina, St George-Hyslop, Peter, Londos, Elisabet, Morgan, Kevin, Lashley, Tammaryn, Warner, Thomas T., Jaunmuktane, Zane, Galasko, Douglas, Santana, Isabel, Tienari, Pentti J., Myllykangas, Liisa, Oinas, Minna, Cairns, Nigel J., Morris, John C., Halliday, Glenda M., Van Deerlin, Vivianna M., Trojanowski, John Q., Grassano, Maurizio, Calvo, Andrea, Mora, Gabriele, Canosa, Antonio, Floris, Gianluca, Bohannan, Ryan C., Brett, Francesca, Gan-Or, Ziv, Geiger, Joshua T., Moore, Anni, May, Patrick, Krüger, Rejko, Goldstein, David S., Lopez, Grisel, Tayebi, Nahid, Sidransky, Ellen, Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Kaufmann, Horacio, Shakkottai, Vikram G., Perkins, Matthew, Newell, Kathy L., Gasser, Thomas, Schulte, Claudia, Landi, Francesco, Salvi, Erika, Cusi, Daniele, Masliah, Eliezer, Kim, Ronald C., Caraway, Chad A., Monuki, Edwin S., Brunetti, Maura, Dawson, Ted M., Rosenthal, Liana S., Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Flanagan, Margaret E., Mao, Qinwen, Bigio, Eileen H., Rodríguez-Rodríguez, Eloy, Infante, Jon, Lage, Carmen, González-Aramburu, Isabel, Sanchez-Juan, Pascual, Ghetti, Bernardino, Keith, Julia, Black, Sandra E., Masellis, Mario, Rogaeva, Ekaterina, Duyckaerts, Charles, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Barrett, Matthew J., Tilley, Bension S., Gentleman, Steve, Logroscino, Giancarlo, Serrano, Geidy E., Beach, Thomas G., McKeith, Ian G., Thomas, Alan J., Attems, Johannes, Morris, Christopher M., Palmer, Laura, Love, Seth, Troakes, Claire, Al-Sarraj, Safa, Hodges, Angela K., Aarsland, Dag, Klein, Gregory, Kaiser, Scott M., Woltjer, Randy, Pastor, Pau, Bekris, Lynn M., Leverenz, James B., Besser, Lilah M., Kuzma, Amanda, Renton, Alan E., Goate, Alison, Bennett, David A., Scherzer, Clemens R., Morris, Huw R., Ferrari, Raffaele, Albani, Diego, Pickering-Brown, Stuart, Faber, Kelley, Kukull, Walter A., Morenas-Rodriguez, Estrella, Lleó, Alberto, Fortea, Juan, Alcolea, Daniel, Clarimon, Jordi, Nalls, Mike A., Ferrucci, Luigi, Resnick, Susan M., Tanaka, Toshiko, Foroud, Tatiana M., Graff-Radford, Neill R., Wszolek, Zbigniew K., Ferman, Tanis, Boeve, Bradley F., Hardy, John A., Topol, Eric J., Torkamani, Ali, Singleton, Andrew B., Ryten, Mina, Dickson, Dennis W., Chiò, Adriano, Ross, Owen A., Gibbs, J. Raphael, Dalgard, Clifton L., Traynor, Bryan J., and Scholz, Sonja W.

Abstract

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s disease and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Published
2021
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18. Action research within an elite rugby union coaching group to influence change in coach learning and pedagogic practice

Author

Chapron, James and Morgan, Kevin

Abstract

ABSTRACTThe aim of this study was to investigate how I, a Welsh regional rugby academy head coach, could utilize practical collaborative action research (CAR) to influence collaboration, learning and pedagogic change within a coaching group. Action research (AR) aims to increase knowledge and improve practice in applied settings and utilises the experiences of the participants as researchers in the field. I acted as head coach and lead researcher with two other professional coaches and two sport science support staff over a three-month period. Data was collected through reflective logs, video observations of training sessions and team meetings. Whilst not without frustrations, difficulties and challenges, qualitative analysis revealed that the coaching team made significant strides in their collaboration, learning and pedagogic practice. Using CAR provided opportunities for the coaching team to develop their motivation, pedagogical knowledge, coaching practice and reflective abilities.Abberivation: CAR - collaborative action research

Published
2020
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19. A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease

Author

Hartl, Daniela, May, Patrick, Gu, Wei, Mayhaus, Manuel, Pichler, Sabrina, Spaniol, Christian, Glaab, Enrico, Bobbili, Dheeraj Reddy, Antony, Paul, Koegelsberger, Sandra, Kurz, Alexander, Grimmer, Timo, Morgan, Kevin, Vardarajan, Badri N., Reitz, Christiane, Hardy, John, Bras, Jose, Guerreiro, Rita, Balling, Rudi, Schneider, Jochen G., and Riemenschneider, Matthias

Abstract

Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that might be explained by rare but functionally important variants. One of the so far identified genes with rare AD causing variants is ADAM10. Using whole-genome sequencing we now identified a single rare nonsynonymous variant (SNV) rs142946965 [p.R215I] in ADAM17co-segregating with an autosomal-dominant pattern of late-onset AD in one family. Subsequent genotyping and analysis of available whole-exome sequencing data of additional case/control samples from Germany, UK, and USA identified five variant carriers among AD patients only. The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to loss-of-function of ADAM17 alpha-secretase. Further, we identified a strong negative correlation between ADAM17and APPgene expression in human brain and present in vitro evidence that ADAM17negatively controls the expression of APP. As a consequence, p.R215I mutation of ADAM17 leads to elevated Aß formation in vitro. Together our data supports a causative association of the identified ADAM17variant in the pathogenesis of AD.

Published
2020
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21. Spatially-resolved investigation of the water inhibition of methane oxidation over palladiumElectronic supplementary information (ESI) available. See DOI: 10.1039/d0cy00154f

Author

Coney, Ciaran, Stere, Cristina, Millington, Paul, Raj, Agnes, Wilkinson, Sam, Caracotsios, Michael, McCullough, Geoffrey, Hardacre, Christopher, Morgan, Kevin, Thompsett, David, and Goguet, Alexandre

Abstract

Pd/Al2O3catalysts are known to be active for the low temperature methane oxidation reactions, however it has been shown that a number of gases normally associated with methane gas streams (H2O, CO2, H2S) can have an inhibitory effect on the total oxidation reaction. This work focuses on the effect of H2O on the complete oxidation of methane on a 3%Pd/Al2O3wash-coated monolith, with a view to understanding the reaction and inhibition mechanisms and their interplay with heat and mass transport phenomena in the monolith. Steady state furnace temperatures of 400 °C, 425 °C and 450 °C, in conjunction with a spatially resolved capillary inlet mass spectrometry (SpaciMS) approach, were employed to test the spatial effect of 0–10% H2O feed concentrations and temperature on complete methane oxidation reactions. 12 sets of experimental intra-catalyst axially resolved gas temperature and concentration profiles were obtained in a central monolith channel and were used to screen a number of postulated global kinetic models, utilising an in house parameter estimation routine developed using Athena Visual Studio v.14.2. A 1D heterogeneous single channel reactor model has been incorporated into the model imposing a gaseous temperature spline to improve the confidence in parameter estimation. The Akaike information criterion (AIC) was used to discriminate between a number of hypothesised global kinetic models, with a newly derived 2 site model demonstrating the best statistical fit.

Published
2020
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23. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W., Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C., Damotte, Vincent, Naj, Adam C., Boland, Anne, Vronskaya, Maria, van der Lee, Sven J., Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R., Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L., Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B., Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N., Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W., Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L., Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V., Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C., Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T., Adams, Hieab H., Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A., Dombroski, Beth A., Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B., Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S., Meslage, Stéphane, Kornhuber, Johannes, White, Charles C., Song, Yuenjoo, Barber, Robert C., Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M., Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L. Adrienne, Albert, Marilyn S., De Deyn, Peter P., Gu, Wei, Himali, Jayanadra J., Beekly, Duane, Squassina, Alessio, Hartmann, Annette M., Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E., Doody, Rachelle S., Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J., Benito, Yolanda A., Holmes, Clive, Karamujić-Čomić, Hata, Frosch, Matthew P., Thonberg, Hakan, Maier, Wolfgang, Roshchupkin, Gennady, Ghetti, Bernardino, Giedraitis, Vilmantas, Kawalia, Amit, Li, Shuo, Huebinger, Ryan M., Kilander, Lena, Moebus, Susanne, Hernández, Isabel, Kamboh, M. Ilyas, Brundin, RoseMarie, Turton, James, Yang, Qiong, Katz, Mindy J., Concari, Letizia, Lord, Jenny, Beiser, Alexa S., Keene, C. Dirk, Helisalmi, Seppo, Kloszewska, Iwona, Kukull, Walter A., Koivisto, Anne Maria, Lynch, Aoibhinn, Tarraga, Lluís, Larson, Eric B., Haapasalo, Annakaisa, Lawlor, Brian, Mosley, Thomas H., Lipton, Richard B., Solfrizzi, Vincenzo, Gill, Michael, Longstreth, W. T., Montine, Thomas J., Frisardi, Vincenza, Diez-Fairen, Monica, Rivadeneira, Fernando, Petersen, Ronald C., Deramecourt, Vincent, Alvarez, Ignacio, Salani, Francesca, Ciaramella, Antonio, Boerwinkle, Eric, Reiman, Eric M., Fievet, Nathalie, Rotter, Jerome I., Reisch, Joan S., Hanon, Olivier, Cupidi, Chiara, Andre Uitterlinden, A. G., Royall, Donald R., Dufouil, Carole, Maletta, Raffaele Giovanni, de Rojas, Itziar, Sano, Mary, Brice, Alexis, Cecchetti, Roberta, George-Hyslop, Peter St, Ritchie, Karen, Tsolaki, Magda, Tsuang, Debby W., Dubois, Bruno, Craig, David, Wu, Chuang-Kuo, Soininen, Hilkka, Avramidou, Despoina, Albin, Roger L., Fratiglioni, Laura, Germanou, Antonia, Apostolova, Liana G., Keller, Lina, Koutroumani, Maria, Arnold, Steven E., Panza, Francesco, Gkatzima, Olymbia, Asthana, Sanjay, Hannequin, Didier, Whitehead, Patrice, Atwood, Craig S., Caffarra, Paolo, Hampel, Harald, Quintela, Inés, Carracedo, Ángel, Lannfelt, Lars, Rubinsztein, David C., Barnes, Lisa L., Pasquier, Florence, Frölich, Lutz, Barral, Sandra, McGuinness, Bernadette, Beach, Thomas G., Johnston, Janet A., Becker, James T., Passmore, Peter, Bigio, Eileen H., Schott, Jonathan M., Bird, Thomas D., Warren, Jason D., Boeve, Bradley F., Lupton, Michelle K., Bowen, James D., Proitsi, Petra, Boxer, Adam, Powell, John F., Burke, James R., Kauwe, John S. K., Burns, Jeffrey M., Mancuso, Michelangelo, Buxbaum, Joseph D., Bonuccelli, Ubaldo, Cairns, Nigel J., McQuillin, Andrew, Cao, Chuanhai, Livingston, Gill, Carlson, Chris S., Bass, Nicholas J., Carlsson, Cynthia M., Hardy, John, Carney, Regina M., Bras, Jose, Carrasquillo, Minerva M., Guerreiro, Rita, Allen, Mariet, Chui, Helena C., Fisher, Elizabeth, Masullo, Carlo, Crocco, Elizabeth A., DeCarli, Charles, Bisceglio, Gina, Dick, Malcolm, Ma, Li, Duara, Ranjan, Graff-Radford, Neill R., Evans, Denis A., Hodges, Angela, Faber, Kelley M., Scherer, Martin, Fallon, Kenneth B., Riemenschneider, Matthias, Fardo, David W., Heun, Reinhard, Farlow, Martin R., Kölsch, Heike, Ferris, Steven, Leber, Markus, Foroud, Tatiana M., Heuser, Isabella, Galasko, Douglas R., Giegling, Ina, Gearing, Marla, Hüll, Michael, Geschwind, Daniel H., Gilbert, John R., Morris, John, Green, Robert C., Mayo, Kevin, Growdon, John H., Feulner, Thomas, Hamilton, Ronald L., Harrell, Lindy E., Drichel, Dmitriy, Honig, Lawrence S., Cushion, Thomas D., Huentelman, Matthew J., Hollingworth, Paul, Hulette, Christine M., Hyman, Bradley T., Marshall, Rachel, Jarvik, Gail P., Meggy, Alun, Abner, Erin, Menzies, Georgina E., Jin, Lee-Way, Leonenko, Ganna, Real, Luis M., Jun, Gyungah R., Baldwin, Clinton T., Grozeva, Detelina, Karydas, Anna, Russo, Giancarlo, Kaye, Jeffrey A., Kim, Ronald, Jessen, Frank, Kowall, Neil W., Vellas, Bruno, Kramer, Joel H., Vardy, Emma, LaFerla, Frank M., Jöckel, Karl-Heinz, Lah, James J., Dichgans, Martin, Leverenz, James B., Mann, David, Levey, Allan I., Pickering-Brown, Stuart, Lieberman, Andrew P., Klopp, Norman, Lunetta, Kathryn L., Wichmann, H-Erich, Lyketsos, Constantine G., Morgan, Kevin, Marson, Daniel C., Brown, Kristelle, Martiniuk, Frank, Medway, Christopher, Mash, Deborah C., Nöthen, Markus M., Masliah, Eliezer, Hooper, Nigel M., McCormick, Wayne C., Daniele, Antonio, McCurry, Susan M., Bayer, Anthony, McDavid, Andrew N., Gallacher, John, McKee, Ann C., van den Bussche, Hendrik, Mesulam, Marsel, Brayne, Carol, Miller, Bruce L., Riedel-Heller, Steffi, Miller, Carol A., Miller, Joshua W., Al-Chalabi, Ammar, Morris, John C., Shaw, Christopher E., Myers, Amanda J., Wiltfang, Jens, O’Bryant, Sid, Olichney, John M., Alvarez, Victoria, Parisi, Joseph E., Singleton, Andrew B., Paulson, Henry L., Collinge, John, Perry, William R., Mead, Simon, Peskind, Elaine, Cribbs, David H., Rossor, Martin, Pierce, Aimee, Ryan, Natalie S., Poon, Wayne W., Nacmias, Benedetta, Potter, Huntington, Sorbi, Sandro, Quinn, Joseph F., Sacchinelli, Eleonora, Raj, Ashok, Spalletta, Gianfranco, Raskind, Murray, Caltagirone, Carlo, Bossù, Paola, Orfei, Maria Donata, Reisberg, Barry, Clarke, Robert, Reitz, Christiane, Smith, A David, Ringman, John M., Warden, Donald, Roberson, Erik D., Wilcock, Gordon, Rogaeva, Ekaterina, Bruni, Amalia Cecilia, Rosen, Howard J., Gallo, Maura, Rosenberg, Roger N., Ben-Shlomo, Yoav, Sager, Mark A., Mecocci, Patrizia, Saykin, Andrew J., Pastor, Pau, Cuccaro, Michael L., Vance, Jeffery M., Schneider, Julie A., Schneider, Lori S., Slifer, Susan, Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Swerdlow, Russell H., Tang, Mitchell, Tanzi, Rudolph E., Trojanowski, John Q., Troncoso, Juan C., Van Deerlin, Vivianna M., Van Eldik, Linda J., Vinters, Harry V., Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Wilhelmsen, Kirk C., Williamson, Jennifer, Wingo, Thomas S., Woltjer, Randall L., Wright, Clinton B., Yu, Chang-En, Yu, Lei, Saba, Yasaman, Pilotto, Alberto, Bullido, Maria J., Peters, Oliver, Crane, Paul K., Bennett, David, Bosco, Paola, Coto, Eliecer, Boccardi, Virginia, De Jager, Phil L., Lleo, Alberto, Warner, Nick, Lopez, Oscar L., Ingelsson, Martin, Deloukas, Panagiotis, Cruchaga, Carlos, Graff, Caroline, Gwilliam, Rhian, Fornage, Myriam, Goate, Alison M., Sanchez-Juan, Pascual, Kehoe, Patrick G., Amin, Najaf, Ertekin-Taner, Nilifur, Berr, Claudine, Debette, Stéphanie, Love, Seth, Launer, Lenore J., Younkin, Steven G., Dartigues, Jean-Francois, Corcoran, Chris, Ikram, M. Arfan, Dickson, Dennis W., Nicolas, Gael, Campion, Dominique, Tschanz, JoAnn, Schmidt, Helena, Hakonarson, Hakon, Clarimon, Jordi, Munger, Ron, Schmidt, Reinhold, Farrer, Lindsay A., Van Broeckhoven, Christine, C. O’Donovan, Michael, DeStefano, Anita L., Jones, Lesley, Haines, Jonathan L., Deleuze, Jean-Francois, Owen, Michael J., Gudnason, Vilmundur, Mayeux, Richard, Escott-Price, Valentina, Psaty, Bruce M., Ramirez, Alfredo, Wang, Li-San, Ruiz, Agustin, van Duijn, Cornelia M., Holmans, Peter A., Seshadri, Sudha, Williams, Julie, Amouyel, Phillippe, Schellenberg, Gerard D., Lambert, Jean-Charles, and Pericak-Vance, Margaret A.

Abstract

Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1,and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer’s or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer’s disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P= 1.32 × 10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Published
2019
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25. Circular Biogas-Based Economy in a Rural Agricultural Setting.

Author

Blades, Luke, Morgan, Kevin, Douglas, Roy, Glover, Stephen, De Rosa, Mattia, Cromie, Thomas, and Smyth, Beatrice

Abstract

This study investigates the application of a circular economy in a rural agricultural setting in Northern Ireland, centered around a typical anaerobic digestion (AD) plant, showing its potential to provide renewable energy for the electricity and transport fuel needs of an average dairy farm and associated milk processing facilities. It was calculated that a typical AD plant has the potential to fuel 22 average sized dairy farms in Northern Ireland, equating to the production, transport, and processing of 51,986 litres of milk per day. The feedstock needs of the AD plant can be provided by the local farming community. [ABSTRACT FROM AUTHOR]

Published
2017
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26. Circular Biogas-Based Economy in a Rural Agricultural Setting.

Author

Blades, Luke, Morgan, Kevin, Douglas, Roy, Glover, Stephen, De Rosa, Mattia, Cromie, Thomas, and Smyth, Beatrice

Abstract

This study investigates the application of a circular economy in a rural agricultural setting in Northern Ireland, centered around a typical anaerobic digestion (AD) plant, showing its potential to provide renewable energy for the electricity and transport fuel needs of an average dairy farm and associated milk processing facilities. It was calculated that a typical AD plant has the potential to fuel 22 average sized dairy farms in Northern Ireland, equating to the production, transport, and processing of 51,986 litres of milk per day. The feedstock needs of the AD plant can be provided by the local farming community. [ABSTRACT FROM AUTHOR]

Published
2017
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28. A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression.

Author

Carrasquillo, Minerva M., Allen, Mariet, Burgess, Jeremy D., Wang, Xue, Strickland, Samantha L., Aryal, Shivani, Siuda, Joanna, Kachadoorian, Michaela L., Medway, Christopher, Younkin, Curtis S., Nair, Asha, Wang, Chen, Chanana, Pritha, Serie, Daniel, Nguyen, Thuy, Lincoln, Sarah, Malphrus, Kimberly G., Morgan, Kevin, Golde, Todd E., and Price, Nathan D.

Abstract

Introduction We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid ( TREM ) gene cluster influence disease through gene expression. Methods Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis. Results A variant within a DNase hypersensitive site 5′ of TREM2 , rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10 −3 and 4.6 × 10 −2 , respectively). Meta-analysis on expression quantitative trait locus results from three independent data sets ( n = 1006) confirmed these associations (uncorrected P = 3.4 × 10 −2 and 3.5 × 10 −3 , Bonferroni-corrected P = 6.7 × 10 −2 and 7.1 × 10 −3 , respectively). Discussion Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome-wide association study meta-analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD. [ABSTRACT FROM AUTHOR]

Published
2017
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29. Social innovation in question: The theoretical and practical implications of a contested concept

Author

Marques, Pedro, Morgan, Kevin, and Richardson, Ranald

Abstract

The concept of social innovation has become pervasive among practitioners and academics, though its definition remains elusive. This paper seeks to address this by suggesting a distinction between structural social innovation, which refers to wide social change in scale and scope, targeted versions of social innovation, which can be either radical or complementary to current socio-economic institutions, and instrumental social innovation, when it is used to rebrand previous agendas in a way that is more appealing to stakeholders. These four types of social innovation are discussed referring to practical examples in the literature. We then explore ways in which the concept could be further developed by engaging with the concepts of socio-technical transitions and the foundational economy.

Published
2018
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30. Intralesional Injection of Collagenase Clostridium histolyticumMay Increase the Risk of Late-Onset Penile Fracture

Author

Beilan, Jonathan A., Wallen, Jared J., Baumgarten, Adam S., Morgan, Kevin N., Parker, Justin L., and Carrion, Rafael E.

Abstract

The use of intralesional injection of collagenase Clostridium histolyticum(CCH) has become a valid treatment option in the management of Peyronie's disease (PD). Multiple studies have shown the drug's safety and efficacy. However, sparse literature exists on the utility of the injection protocol's 14-day “observation period,” in which patients are instructed to abstain from all sexual activity.

Published
2018
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31. Physical education in Taiwan: when students begin to take control.

Author

Sproule, John, Ching-Ping Lin, Martindale, Russell, and Morgan, Kevin

Abstract

The aim of this study was to investigate the effect on self-regulated learning (SRL) of a physical education (PE) pedagogy based on Zimmerman's (2000) model of SRL by means of an 8-week PE curriculum intervention in Taiwan. Participants were 632 Taiwanese students (aged 13.9 ±0.3 years; 28 PE classes) and a wait list control class (n = 21; aged 14.1 ±0.2 years). Constructs from the Intrinsic Motivation Inventory, the Motivated Strategies for Learning Questionnaire, and the Five Component Scale for Self-Regulation were measured pre-and post the intervention by means of on an online survey platform. Multiple repeated measures ANOVAs were used to determine if there were any significant differences pre- and post the intervention and any interaction effects between the intervention and the control. The classes who participated in the intervention showed relatively small mean increases in enjoyment, perceived competence, intrinsic value, self-efficacy, cognitive strategy use, goal setting, strategy implementation and strategy monitoring. In contrast for the control class, eight out of the eleven factors showed relatively larger negative changes in scores. These data indicate that with this sample the benefits of adopting a selfregulated learning approach in PE lessons over an 8-week period appeared to be more about maintenance of the stability of these personal characteristics rather than the enhancement of them. [ABSTRACT FROM AUTHOR]

Published
2017
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32. Chapter Three - In Situ Spatially Resolved Techniques for the Investigation of Packed Bed Catalytic Reactors: Current Status and Future Outlook of Spaci-FB.

Author

Goguet, Alexandre, Stewart, Caomhán, Touitou, Jamal, and Morgan, Kevin

Abstract

Over the past two decades a large effort has been dedicated to the development and optimization of techniques aimed at resolving the evolution of the chemistry within structured catalysts such as monoliths or foams under operando conditions. This approach, known as spatial resolution, is a powerful tool in the unraveling of complex reaction networks, as well as kinetic characterization. The most recent developments have been made at providing such spatial resolution at the early stages of the catalyst development, i.e., when the catalyst is still in its powdered form. Techniques aimed at providing spatial resolutions of the gas composition, of structural information, and of adsorbate distributions via X-ray and vibrational-based spectroscopies, respectively, are developing rapidly. The ability to simultaneously operate these spatially resolved approaches has the potential of providing a powerful platform for reaction mechanism investigations. Herein, we discuss and evaluate the development of a spatially resolved technique for powdered catalysts developed at Queen's University Belfast, namely the Spaci-FB. Furthermore, some aims and aspirations for further evolution of spatially resolved techniques are presented. [ABSTRACT FROM AUTHOR]

Published
2017
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33. Methylation Profiling RIN3 and MEF2C Identifies Epigenetic Marks Associated with Sporadic Early Onset Alzheimer’s Disease

Author

Boden, Kirsty A., Barber, Imelda S., Clement, Naomi, Patel, Tulsi, Guetta-Baranes, Tamar, Brookes, Keeley J., Chappell, Sally, Craigon, Jim, Chapman, Natalie H., Morgan, Kevin, Seymour, Graham B., and Bottley, Andrew

Abstract

A number of genetic loci associate with early onset Alzheimer’s disease (EOAD); however, the drivers of this disease remains enigmatic. Genome wide association and in vivomodeling have shown that loss-of-function, e.g., ABCA7, reduced levels of SIRT1 and MEFF2C, or increased levels of PTK2ß confer risk or link to the pathogenies. It is known that DNA methylation can profoundly affect gene expression and can impact on the composition of the proteome; therefore, the aim of this study is to assess if genes associated with sporadic EOAD (sEOAD) are differentially methylated. Epi-profiles of DNA extracted from blood and cortex were compared using a pyrosequencing platform. We identified significant group-wide hypomethylation in AD blood when compared to controls for 7 CpGs located within the 3’UTR of RIN3 (CpG1 p?=?0.019, CpG2 p?=?0.018, CpG3 p?=?0.012, CpG4 p?=?0.009, CpG5 p?=?0.002, CpG6 p?=?0.018, and CpG7 p?=?0.013, respectively; AD/Control n?=?22/26; Male/Female n?=?27/21). Observed effects were not gender specific. No group wide significant differences were found in the promoter methylation of PTK2ß, ABCA7, SIRT1, or MEF2C,genes known to associate with late onset AD. A rare and significant difference in methylation was observed for one CpG located upstream of the MEF2Cpromoter in one AD individual only (22% reduction in methylation, p?=?2.0E-10; Control n?=?26, AD n?=?25, Male/Female n?=?29/22). It is plausible aberrant methylation may mark sEOAD in blood and may manifest in some individuals as rare epi-variants for genes linked to sEOAD.

Published
2017
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34. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author

Sims, Rebecca, van der Lee, Sven J, Naj, Adam C, Bellenguez, Céline, Badarinarayan, Nandini, Jakobsdottir, Johanna, Kunkle, Brian W, Boland, Anne, Raybould, Rachel, Bis, Joshua C, Martin, Eden R, Grenier-Boley, Benjamin, Heilmann-Heimbach, Stefanie, Chouraki, Vincent, Kuzma, Amanda B, Sleegers, Kristel, Vronskaya, Maria, Ruiz, Agustin, Graham, Robert R, Olaso, Robert, Hoffmann, Per, Grove, Megan L, Vardarajan, Badri N, Hiltunen, Mikko, Nöthen, Markus M, White, Charles C, Hamilton-Nelson, Kara L, Epelbaum, Jacques, Maier, Wolfgang, Choi, Seung-Hoan, Beecham, Gary W, Dulary, Cécile, Herms, Stefan, Smith, Albert V, Funk, Cory C, Derbois, Céline, Forstner, Andreas J, Ahmad, Shahzad, Li, Hongdong, Bacq, Delphine, Harold, Denise, Satizabal, Claudia L, Valladares, Otto, Squassina, Alessio, Thomas, Rhodri, Brody, Jennifer A, Qu, Liming, Sánchez-Juan, Pascual, Morgan, Taniesha, Wolters, Frank J, Zhao, Yi, Garcia, Florentino Sanchez, Denning, Nicola, Fornage, Myriam, Malamon, John, Naranjo, Maria Candida Deniz, Majounie, Elisa, Mosley, Thomas H, Dombroski, Beth, Wallon, David, Lupton, Michelle K, Dupuis, Josée, Whitehead, Patrice, Fratiglioni, Laura, Medway, Christopher, Jian, Xueqiu, Mukherjee, Shubhabrata, Keller, Lina, Brown, Kristelle, Lin, Honghuang, Cantwell, Laura B, Panza, Francesco, McGuinness, Bernadette, Moreno-Grau, Sonia, Burgess, Jeremy D, Solfrizzi, Vincenzo, Proitsi, Petra, Adams, Hieab H, Allen, Mariet, Seripa, Davide, Pastor, Pau, Cupples, L Adrienne, Price, Nathan D, Hannequin, Didier, Frank-García, Ana, Levy, Daniel, Chakrabarty, Paramita, Caffarra, Paolo, Giegling, Ina, Beiser, Alexa S, Giedraitis, Vilmantas, Hampel, Harald, Garcia, Melissa E, Wang, Xue, Lannfelt, Lars, Mecocci, Patrizia, Eiriksdottir, Gudny, Crane, Paul K, Pasquier, Florence, Boccardi, Virginia, Henández, Isabel, Barber, Robert C, Scherer, Martin, Tarraga, Lluis, Adams, Perrie M, Leber, Markus, Chen, Yuning, Albert, Marilyn S, Riedel-Heller, Steffi, Emilsson, Valur, Beekly, Duane, Braae, Anne, Schmidt, Reinhold, Blacker, Deborah, Masullo, Carlo, Schmidt, Helena, Doody, Rachelle S, Spalletta, Gianfranco, Jr, W T Longstreth, Fairchild, Thomas J, Bossù, Paola, Lopez, Oscar L, Frosch, Matthew P, Sacchinelli, Eleonora, Ghetti, Bernardino, Yang, Qiong, Huebinger, Ryan M, Jessen, Frank, Li, Shuo, Kamboh, M Ilyas, Morris, John, Sotolongo-Grau, Oscar, Katz, Mindy J, Corcoran, Chris, Dunstan, Melanie, Braddel, Amy, Thomas, Charlene, Meggy, Alun, Marshall, Rachel, Gerrish, Amy, Chapman, Jade, Aguilar, Miquel, Taylor, Sarah, Hill, Matt, Fairén, Mònica Díez, Hodges, Angela, Vellas, Bruno, Soininen, Hilkka, Kloszewska, Iwona, Daniilidou, Makrina, Uphill, James, Patel, Yogen, Hughes, Joseph T, Lord, Jenny, Turton, James, Hartmann, Annette M, Cecchetti, Roberta, Fenoglio, Chiara, Serpente, Maria, Arcaro, Marina, Caltagirone, Carlo, Orfei, Maria Donata, Ciaramella, Antonio, Pichler, Sabrina, Mayhaus, Manuel, Gu, Wei, Lleó, Alberto, Fortea, Juan, Blesa, Rafael, Barber, Imelda S, Brookes, Keeley, Cupidi, Chiara, Maletta, Raffaele Giovanni, Carrell, David, Sorbi, Sandro, Moebus, Susanne, Urbano, Maria, Pilotto, Alberto, Kornhuber, Johannes, Bosco, Paolo, Todd, Stephen, Craig, David, Johnston, Janet, Gill, Michael, Lawlor, Brian, Lynch, Aoibhinn, Fox, Nick C, Hardy, John, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Baldwin, Clinton T, Barnes, Lisa L, Barral, Sandra, Beach, Thomas G, Becker, James T, Bigio, Eileen H, Bird, Thomas D, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Burns, Jeffrey M, Buxbaum, Joseph D, Cairns, Nigel J, Cao, Chuanhai, Carlson, Chris S, Carlsson, Cynthia M, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Diaz, Carolina Ceballos, Chui, Helena C, Clark, David G, Cribbs, David H, Crocco, Elizabeth A, DeCarli, Charles, Dick, Malcolm, Duara, Ranjan, Evans, Denis A, Faber, Kelley M, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Gilbert, John R, Graff-Radford, Neill R, Green, Robert C, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Honig, Lawrence S, Huentelman, Matthew J, Hulette, Christine M, Hyman, Bradley T, Jarvik, Gail P, Abner, Erin, Jin, Lee-Way, Jun, Gyungah, Karydas, Anna, Kaye, Jeffrey A, Kim, Ronald, Kowall, Neil W, Kramer, Joel H, LaFerla, Frank M, Lah, James J, Leverenz, James B, Levey, Allan I, Li, Ge, Lieberman, Andrew P, Lunetta, Kathryn L, Lyketsos, Constantine G, Marson, Daniel C, Martiniuk, Frank, Mash, Deborah C, Masliah, Eliezer, McCormick, Wayne C, McCurry, Susan M, McDavid, Andrew N, McKee, Ann C, Mesulam, Marsel, Miller, Bruce L, Miller, Carol A, Miller, Joshua W, Morris, John C, Murrell, Jill R, Myers, Amanda J, O'Bryant, Sid, Olichney, John M, Pankratz, Vernon S, Parisi, Joseph E, Paulson, Henry L, Perry, William, Peskind, Elaine, Pierce, Aimee, Poon, Wayne W, Potter, Huntington, Quinn, Joseph F, Raj, Ashok, Raskind, Murray, Reisberg, Barry, Reitz, Christiane, Ringman, John M, Roberson, Erik D, Rogaeva, Ekaterina, Rosen, Howard J, Rosenberg, Roger N, Sager, Mark A, Saykin, Andrew J, Schneider, Julie A, Schneider, Lon S, Seeley, William W, Smith, Amanda G, Sonnen, Joshua A, Spina, Salvatore, Stern, Robert A, Swerdlow, Russell H, Tanzi, Rudolph E, Thornton-Wells, Tricia A, Trojanowski, John Q, Troncoso, Juan C, Van Deerlin, Vivianna M, Van Eldik, Linda J, Vinters, Harry V, Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A, Wilhelmsen, Kirk C, Williamson, Jennifer, Wingo, Thomas S, Woltjer, Randall L, Wright, Clinton B, Yu, Chang-En, Yu, Lei, Garzia, Fabienne, Golamaully, Feroze, Septier, Gislain, Engelborghs, Sebastien, Vandenberghe, Rik, De Deyn, Peter P, Fernadez, Carmen Muñoz, Benito, Yoland Aladro, Thonberg, Hakan, Forsell, Charlotte, Lilius, Lena, Kinhult-Stählbom, Anne, Kilander, Lena, Brundin, RoseMarie, Concari, Letizia, Helisalmi, Seppo, Koivisto, Anne Maria, Haapasalo, Annakaisa, Dermecourt, Vincent, Fievet, Nathalie, Hanon, Olivier, Dufouil, Carole, Brice, Alexis, Ritchie, Karen, Dubois, Bruno, Himali, Jayanadra J, Keene, C Dirk, Tschanz, JoAnn, Fitzpatrick, Annette L, Kukull, Walter A, Norton, Maria, Aspelund, Thor, Larson, Eric B, Munger, Ron, Rotter, Jerome I, Lipton, Richard B, Bullido, María J, Hofman, Albert, Montine, Thomas J, Coto, Eliecer, Boerwinkle, Eric, Petersen, Ronald C, Alvarez, Victoria, Rivadeneira, Fernando, Reiman, Eric M, Gallo, Maura, O'Donnell, Christopher J, Reisch, Joan S, Bruni, Amalia Cecilia, Royall, Donald R, Dichgans, Martin, Sano, Mary, Galimberti, Daniela, St George-Hyslop, Peter, Scarpini, Elio, Tsuang, Debby W, Mancuso, Michelangelo, Bonuccelli, Ubaldo, Winslow, Ashley R, Daniele, Antonio, Wu, Chuang-Kuo, Peters, Oliver, Nacmias, Benedetta, Riemenschneider, Matthias, Heun, Reinhard, Brayne, Carol, Rubinsztein, David C, Bras, Jose, Guerreiro, Rita, Al-Chalabi, Ammar, Shaw, Christopher E, Collinge, John, Mann, David, Tsolaki, Magda, Clarimón, Jordi, Sussams, Rebecca, Lovestone, Simon, O'Donovan, Michael C, Owen, Michael J, Behrens, Timothy W, Mead, Simon, Goate, Alison M, Uitterlinden, Andre G, Holmes, Clive, Cruchaga, Carlos, Ingelsson, Martin, Bennett, David A, Powell, John, Golde, Todd E, Graff, Caroline, De Jager, Philip L, Morgan, Kevin, Ertekin-Taner, Nilufer, Combarros, Onofre, Psaty, Bruce M, Passmore, Peter, Younkin, Steven G, Berr, Claudine, Gudnason, Vilmundur, Rujescu, Dan, Dickson, Dennis W, Dartigues, Jean-François, DeStefano, Anita L, Ortega-Cubero, Sara, Hakonarson, Hakon, Campion, Dominique, Boada, Merce, Kauwe, John Keoni, Farrer, Lindsay A, Van Broeckhoven, Christine, Ikram, M Arfan, Jones, Lesley, Haines, Jonathan L, Tzourio, Christophe, Launer, Lenore J, Escott-Price, Valentina, Mayeux, Richard, Deleuze, Jean-François, Amin, Najaf, Holmans, Peter A, Pericak-Vance, Margaret A, Amouyel, Philippe, van Duijn, Cornelia M, Ramirez, Alfredo, Wang, Li-San, Lambert, Jean-Charles, Seshadri, Sudha, Williams, Julie, and Schellenberg, Gerard D

Abstract

We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases= 0.0059, MAFcontrols= 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases= 0.011, MAFcontrols= 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases= 0.0143, MAFcontrols= 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Published
2017
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35. Nurturing novelty: Regional innovation policy in the age of smart specialisation

Author

Morgan, Kevin

Abstract

Smart specialisation is the most ambitious regional innovation programme ever to be launched in the European Union and it affords a unique opportunity to explore the interplay between institutions, innovation and development. The article argues that smart specialisation makes unprecedented demands on public sector bodies to nurture more collaborative forms of economic search and craft more inclusive forms of regional governance. To explore these issues with the granularity they deserve, the article offers detailed case studies of two regional innovation policy repertoires in Wales and the Basque Country, where it is argued that the ‘old industrial region’ moniker conceals as much as it reveals because, for all their apparent similarities, they have pursued very different repertoires. The article concludes on a more general note by suggesting how regional innovation studies could be enriched by engaging with theoretical perspectives from other fields.

Published
2017
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37. Targeted bisulfite sequencing analysis of candidate genes associated with Alzheimer's disease.

Author

Wheildon, Greg, Smith, Adam R., Soanes, Darren, Smith, Rebecca G., Moore, Karen, O'Neill, Paul, Morgan, Kevin, Thomas, Alan J, Francis, Paul T, Love, Seth, Mill, Jonathan, Pishva, Ehsan, and Lunnon, Katie

Abstract

Background: Recent epigenome‐wide association studies (EWAS) have identified a number of loci in specific genes that show robust and reproducible alterations in DNA methylation in Alzheimer's disease brain samples. The standard method to assess methylation in EWAS is via microarrays, however, these only target a limited number of methylation sites in each gene. Therefore, further analysis of methylation changes across the entire gene are required to determine the exact extent and pattern of methylation changes in disease. In this study we have performed targeted bisulfite sequencing for candidate genes in the Brains for Dementia Research (BDR) tissue sample resource, which is a highly characterized cohort containing tissue with a high degree of standardized pathological, clinical and administrative data available to allow comparative studies. Method: Prefrontal cortex brain samples from 60 individuals were selected from the BDR cohort and grouped by Braak stage (Control 0‐II; mild cognitive impairment III‐IV; AD V‐VI). The DNA was extracted, before 30 genomic regions of interest, identified from previous AD EWAS, were captured using Agilent Sure Select target baits. The DNA was next‐generation bisulfite sequenced, before the sequence reads were aligned and the methylation status of cytosine residues were called using the Bismark Bisulfite Mapper program. Differentially methylated positions (DMPs) were then analyzed across the three groups. Result: The degree and extent of methylation within the targeted genomic regions were identified and quantified for each group before being analyzed using linear regression models. Conclusion: This study builds on previous work that identified differential methylation in several genomic regions that were associated with Braak stage. By identifying the exact positions that are subjected to differential methylation this work provides further evidence that dysregulation of methylation is associated with pathological changes in AD prefrontal cortex. [ABSTRACT FROM AUTHOR]

Published
2022
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39. Reconceptualizing Motivational Climate in Physical Education and Sport Coaching: An Interdisciplinary Perspective

Author

Morgan, Kevin

Abstract

ABSTRACTThe purpose of this article is to re-conceptualize the phenomenon of motivational climate in Physical Education and sport coaching as a concept that is not purely psychological in nature, but also highly dependent upon pedagogical and sociological theories. In doing so, an interdisciplinary perspective is promoted where the three aforementioned disciplines combine and intersect in order to enrich teachers’ and coaches’ understanding of motivational climate. The ultimate aim is to assist practitioners in fostering an effective and stimulating learning environment. The pre-existing TARGET acronym (task, authority, recognition, grouping, evaluation and time) is used to structure the paper. These TARGET structures are further developed with links to relevant pedagogical and sociological theory to enrich them. Further, a strong emphasis is placed on ‘relationships,’ which have not previously been featured in the TARGET literature. It is anticipated that inter-disciplinary research on motivational climate will emerge from the ideas presented.

Published
2017
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40. The Politics of the Public Plate: School Food and Sustainability.

Author

MORGAN, KEVIN

Subjects
SCHOOL food, NUTRITION for school children, GOVERNMENT purchasing, SUSTAINABILITY
Abstract

The article discusses the politics of school food and sustainability in Great Britain. Topics include the multifunctional capacity of food, the power of public food procurement, the Department for Environment, Food and Rural Affairs (DEFRA) definitions of the sustainable public plate, and the initiatives in creative and sustainable public food procurement.

Published
2014

42. Evaluation of Improvements to the Student Experience in Chemical Engineering Practical Classes: From Prelaboratories to Postlaboratories

Author

Morgan, Kevin

Abstract

Practical classes are an important and essential part of undergraduate programs in Chemical Engineering, as each experiment provides an opportunity to reinforce the theory of discrete unit operations that are taught elsewhere in the course. While an expensive pedagogical method, when practical sessions are delivered well, they can be one of the best learning experiences for students. As with all pedagogical methods, for students to gain maximum benefit of practical classes, a high level of engagement is required. Consequently, lab assignments need to be designed in a way that guides and instructs students on the theory, procedure, and risks associated with any practical and its associated assessments. This paper describes the outcomes of a qualitative investigation that evaluated student perceptions of updated prelab content combined with a new variation in postlab assessments and a renewed focus on practical skills during practical classes. The overall aim was to improve the student experience in practical classes. Paradoxically, periods of remote teaching enforced by the COVID-19 pandemic created further opportunities to make innovative changes to practical class resources. Subsequent student evaluations also indicated perceptions about each newly introduced component (instructional videos, online multiple-choice prelab quiz, variation in postlab assessment, introduction of grading rubrics, and a practical skills assessment), and more than 75% wanted these resources retained.

Published
2023
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43. A Fluorescence Resonance Energy Transfer Assay For Monitoring ?- Synclein Aggregation in a Caenorhabditis Elegans Model For Parkinson's Disease

Author

Nagarajan, Archana, Bodhicharla, Rakesh, Winter, Jody, Anbalagan, Charumathi, Morgan, Kevin, Searle, Mark, Nazir, Aamir, Adenle, Ademola, Fineberg, April, Brady, Declan, Vere, Kelly, Richens, Jo, O';Shea, Paul, Bell, David, and de-Pomerai, David

Abstract

The aggregation of ?-synuclein (Syn or S) to form insoluble fibrils is important in the pathogenesis of Parkinson's disease, but key risk factors remain ill-defined. We have developed Fluorescence Resonance Energy Transfer (FRET)-based assays for ?-synuclein aggregation, using Green Fluorescent Protein variants Cerulean (C) or Venus (V), fused to each other (CV, VC) or to human synuclein (SC, SV etc). Bacterially expressed proteins were purified to homogeneity, and C-terminal fusions SC and SV largely retained their ability to aggregate in vitro. FRET signals from mixtures of SC and SV were used to monitor aggregation. These fusion genes were linked to the C. elegans unc-54 myosin promoter to generate integrated transgenic strains. Increased FRET signals, indicative of S aggregation, were observed following treatment of unc-54::SC + unc-54::SV double transgenic worms with low concentrations of mercury or chlorpyrifos, or with RNAi against hsp-70 and hip-1. Opposite changes in Yellow Fluorescent Protein (YFP) fluorescence in an unc-54::SV strain (NL5901) are likely to reflect FRET from Yellow Fluorescent Protein to aggregates of Syn fusion protein. This could provide the basis for a high throughput screening assay, which could be used for studying the effects of toxic chemicals and environmental pollutants on the aggregation of proteins such as Syn in vivo.

Published
2015

44. Re-dispersion of gold supported on a ‘mixed’oxide support

Author

Morgan, Kevin, Burch, Robbie, Daous, Muhammad, Delgado, Juan-José, Goguet, Alexandre, Hardacre, Christopher, Petrov, Lachezar A., and Rooney, David W.

Abstract

The ability to reactivate, stabilize and increase the lifetime of gold catalysts by dispersing large, inactive gold nanoparticles to smaller nanoparticles provides an opportunity to make gold catalysts more practical for industrial applications. Previously it has been demonstrated that mild treatment with iodomethane (J. Am. Chem. Soc., 2009, 131, 6973; Angew. Chem. Int. Ed., 2011, 50, 8912) was able to re-disperse gold on carbon and metal oxide supports. In the current work, we show that this technique can be applied to re-disperse gold on a ‘mixed’ metal oxide, namely a mechanical mixture of ceria, zirconia and titania. Characterization was conducted to guage the impact of the iodomethane (CH3I) treatment on a previously sintered catalyst.

Published
2015
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45. Coach development through collaborative action research: enhancing the learning environment within a national talent development system

Author

Clements, Dan and Morgan, Kevin

Abstract

AbstractMotivation to learn is an essential factor of talent being realised , which throws into light the essential role that the motivational climate plays in developing talent. Through collaborative action research, the aim of this study was to develop coaches’ learning to enhance the learning environment within a national talent development system, utilising the) TARGET framework (task, authority, recognition, grouping, evaluation and time). Results revealed that participatory collaborative action research is an effective coach development tool for coaches in order to enhance their learning and the motivational climate within their sessions. The study identified the benefits of coach development through participatory action research, revealing a highly positive response to the role that collaborative learning played in pedagogical development.

Published
2015
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48. The occupational impact of sleep quality and insomnia symptoms.

Author

Kucharczyk, Erica R., Morgan, Kevin, and Hall, Andrew P.

Abstract

Summary: While the importance of assessing the occupational consequences of insomnia is emphasized in clinical nosologies and research guidelines, there is little consensus on which aspects of occupational performance should be assessed, the most methodologically justifiable measures of insomnia and work performance, and how outcomes should be reported. The present review was designed to summarize and methodologically critique the assessment of those aspects of occupational performance most impacted by (or most frequently associated with) insomnia symptoms. The 30 studies which met the review inclusion criteria broadly addressed six domains of occupational functioning: absenteeism; workplace accidents; productivity; punctuality; job satisfaction and career progression. Collectively, study outcomes support the conclusions that insomnia symptoms: are consistently associated with excess absenteeism; elevate accident risk in the workplace; reduce subjectively experienced workplace productivity (at least in the shorter term); inhibit career progression; and can degrade job satisfaction. Study outcomes do not support the conclusion that people with insomnia are significantly less punctual than other workers. The overall value of the occupational sleep-health literature, however, is limited by a lack of comparability among studies. In particular, there is a clear need to standardize definitions of sleep and occupational outcomes, and to recognize the confounding influence of health variables on occupational performance and sleep. [Copyright &y& Elsevier]

Published
2012
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49. «Multiplexité» et/ou multiplicité? Regards comparatifs sur la biographie collective du communisme britannique.

Author

Morgan, Kevin

Abstract

The article presents an overview of the evolution of the historiography of British Communism and compares it to the evolution of French Communism. It discusses the lack of interest in research related to this topics during the 1980s, the biographical dictionary focusing on the French labor movement "Dictionnaire biographique du mouvement ouvrier français" also called "Maitron," edited by Jean Maitron, and the dictionary "Dictionary of Labour Biography," written by John Saville. Topics of discussion include the British and French Communist parties Parti communiste de Grande-Bretagne (PCGB) and the Parti communiste français (PCF).

Published
2011
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50. Problem-based and experiential learning: Engaging students in an undergraduate physical education module.

Author

Bethell, Sally and Morgan, Kevin

Subjects
PROBLEM-based learning, EXPERIENTIAL learning, UNDERGRADUATE education, PHYSICAL education, MODULARITY (Grammar), TEACHING methods
Abstract

The aim of this study was to employ a combined problem-based learning (PBL) and experiential learning theory (ELT) methodology as a means of engaging students on an undergraduate physical education (PE) and sport pedagogy module. Focus groups were conducted to investigate the students' and tutors' responses to the teaching approach. The results indicated that the method of teaching was associated with students feeling confident about their critical knowledge and understanding of contemporary issue in PE, their presentation and discussion skills, and a positive engagement with the module. Overall the approach was highly beneficial to the student learning experience. [ABSTRACT FROM AUTHOR]

Published
2011
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