11 results on '"Arnold, Corey R."'
Search Results
2. Hox ‐driven conditional immortalization of myeloid and lymphoid progenitors: Uses, advantages, and future potential
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Lail, Shranjit S., primary, Arnold, Corey R., additional, de Almeida, Luiz G. N., additional, McKenna, Neil, additional, Chiriboga, Jose A., additional, Dufour, Antoine, additional, Warren, Amy L., additional, and Yates, Robin Michael, additional
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- 2022
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3. Stroke-associated intergenic variants modulate a human FOXF2 transcriptional enhancer
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Ryu, Jae-Ryeon, primary, Ahuja, Suchit, additional, Arnold, Corey R., additional, Potts, Kyle G., additional, Mishra, Aniket, additional, Yang, Qiong, additional, Sargurupremraj, Muralidharan, additional, Mahoney, Douglas J., additional, Seshadri, Sudha, additional, Debette, Stéphanie, additional, and Childs, Sarah J., additional
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- 2022
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4. Mutation of FOXC1 and PITX2 induces cerebral small-vessel disease
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French, Curtis R., Seshadri, Sudha, Destefano, Anita L., Fornage, Myriam, Arnold, Corey R., Gage, Philip J., Skarie, Jonathan M., Dobyns, William B., Millen, Kathleen J., Liu, Ting, Dietz, William, Kume, Tsutomu, Hofker, Marten, Emery, Derek J., Childs, Sarah J., Waskiewicz, Andrew J., and Lehmann, Ordan J.
- Subjects
Magnetic resonance imaging -- Usage ,Single nucleotide polymorphisms -- Research ,Cerebrovascular disease -- Risk factors -- Genetic aspects -- Research -- Diagnosis ,Health care industry - Abstract
Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXCI-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine [Pitx2.sup.-/-] mutants displayed brain vascular phenotypes. Together, these results extend the genetic etiology of stroke and demonstrate an increasing developmental basis for human cerebrovascular disease., Introduction Stroke is a leading cause of morbidity and mortality, whose prevalence increases dramatically with age. Despite its substantial heritable basis, only a small number of causative genes have so [...]
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- 2014
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5. Extracellular cathepsin Z signals through the α5 integrin and augments NLRP3 inflammasome activation
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Campden, Rhiannon I., primary, Warren, Amy L., additional, Greene, Catherine J., additional, Chiriboga, Jose A., additional, Arnold, Corey R., additional, Aggarwal, Devin, additional, McKenna, Neil, additional, Sandall, Christina F., additional, MacDonald, Justin A., additional, and Yates, Robin M., additional
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- 2021
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6. Stroke-associated intergenic variants modulate a human FOXF2 transcriptional enhancer.
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Jae-Ryeon Ryu, Ahuja, Suchit, Arnold, Corey R., Potts, Kyle G., Mishra, Aniket, Qiong Yang, Sargurupremraj, Muralidharan, Mahoney, Douglas J., Seshadri, Sudha, Debette, Stéphanie, and Childs, Sarah J.
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FORKHEAD transcription factors ,BINDING sites ,GENE expression ,ISCHEMIC stroke ,WHITE matter (Nerve tissue) - Abstract
SNPs associated with human stroke risk have been identified in the intergenic region between Forkhead family transcription factors FOXF2 and FOXQ1, but we lack amechanism for the association. FoxF2 is expressed in vascular mural pericytes and is important for maintaining pericyte number and stabilizing small vessels in zebrafish. The stroke-associated SNPs are located in a previously unknown transcriptional enhancer for FOXF2, functional in human cells and zebrafish. We identify critical enhancer regions for FOXF2 gene expression, including binding sites occupied by transcription factors ETS1, RBPJ, and CTCF. rs74564934, a stroke-associated SNP adjacent to the ETS1 binding site, decreases enhancer function, as does mutation of RPBJ sites. rs74564934 is significantly associated with the increased risk of any stroke, ischemic stroke, small vessel stroke, and elevated white matter hyperintensity burden in humans. Foxf2 has a conserved function cross-species and is expressed in vascular mural pericytes of the vessel wall. Thus, stroke-associated SNPs modulate enhancer activity and expression of a regulator of vascular stabilization, FOXF2, thereby modulating stroke risk. [ABSTRACT FROM AUTHOR]
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- 2022
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7. A non-immunological role for γ-interferon–inducible lysosomal thiol reductase (GILT) in osteoclastic bone resorption
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Ewanchuk, Benjamin W., primary, Arnold, Corey R., additional, Balce, Dale R., additional, Premnath, Priyatha, additional, Orsetti, Tanis L., additional, Warren, Amy L., additional, Olsen, Alexandra, additional, Krawetz, Roman J., additional, and Yates, Robin M., additional
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- 2021
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8. Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies
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Chauhan, Ganesh, Arnold, Corey R., Chu, Audrey Y., Fornage, Myriam, Reyahi, Azadeh, Bis, Joshua C., Havulinna, Aki S., Sargurupremraj, Muralidharan, Smith, Albert Vernon, Adams, Hieab H. H., Choi, Seung Hoan, Pulit, Sara L., Trompet, Stella, Garcia, Melissa E., Manichaikul, Ani, Teumer, Alexander, Gustafsson, Stefan, Bartz, Traci M., Bellenguez, Céline, Vidal, Jean Sebastien, Jian, Xueqiu, Kjartansson, Olafur, Wiggins, Kerri L., Satizabal, Claudia L., Xue, Flora, Ripatti, Samuli, Liu, Yongmei, Deelen, Joris, den Hoed, Marcel, Bevan, Steve, Hopewell, Jemma C., Malik, Rainer, Heckbert, Susan R., Rice, Kenneth, Smith, Nicholas L., Levi, Christopher, Sharma, Pankaj, Sudlow, Cathie LM, Nik, Ali Moussavi, Cole, John W., Schmidt, Reinhold, Meschia, James, Thijs, Vincent, Lindgren, Arne, Melander, Olle, Grewal, Raji P., Sacco, Ralph L., Rundek, Tatjana, Rothwell, Peter M., Arnett, Donna K., Jern, Christina, Johnson, Julie A., Benavente, Oscar R., Wassertheil-Smoller, Sylvia, Lee, Jin-Moo, Wong, Quenna, Aparicio, Hugo J., Engelter, Stefan T., Kloss, Manja, Leys, Didier, Pezzini, Alessandro, Buring, Julie E., Ridker, Paul M., Berr, Claudine, Dartigues, Jean-François, Hamsten, Anders, Magnusson, Patrik K., Traylor, Matthew, Pedersen, Nancy L., Lannfelt, Lars, Lindgren, Lars, Lindgren, Cecilia M., Morris, Andrew P., Jimenez-Conde, Jordi, Montaner, Joan, Radmanesh, Farid, Slowik, Agnieszka, Woo, Daniel, Hofman, Albert, Koudstaal, Peter J., Portegies, Marileen L. P., Uitterlinden, André G., de Craen, Anton J. M., Ford, Ian, Jukema, J. Wouter, Stott, David J., Allen, Norrina B., Sale, Michele M., Johnson, Andrew D., Bennett, David A., De Jager, Philip L., White, Charles C., Grabe, Hans Jörgen, Markus, Marcello Ricardo Paulista, Schminke, Ulf, Boncoraglio, Giorgio B., Clarke, Robert, Kamatani, Yoichiro, Dallongeville, Jean, Lopez, Oscar L., Rotter, Jerome I., Nalls, Michael A., Gottesman, Rebecca F., Griswold, Michael E., Knopman, David S., Windham, B. Gwen, Beiser, Alexa, Markus, Hugh S., Vartiainen, Erkki, French, Curtis R., Dichgans, Martin, Pastinen, Tomi, Lathrop, Mark, Gudnason, Vilmundur, Kurth, Tobias, Psaty, Bruce M., Harris, Tamara B., Rich, Stephen S., deStefano, Anita L., Schmidt, Carsten Oliver, Worrall, Bradford B., Rosand, Jonathan, Salomaa, Veikko, Mosley, Thomas H., Ingelsson, Erik, van Duijn, Cornelia M., Tzourio, Christophe, Rexrode, Kathryn M., Lehmann, Ordan J., Launer, Lenore J., Ikram, M. Arfan, Carlsson, Peter, Chasman, Daniel I., Childs, Sarah J., Longstreth, William T., Seshadri, Sudha, Debette, Stéphanie, Chauhan, Ganesh, Arnold, Corey R., Chu, Audrey Y., Fornage, Myriam, Reyahi, Azadeh, Bis, Joshua C., Havulinna, Aki S., Sargurupremraj, Muralidharan, Smith, Albert Vernon, Adams, Hieab H. H., Choi, Seung Hoan, Pulit, Sara L., Trompet, Stella, Garcia, Melissa E., Manichaikul, Ani, Teumer, Alexander, Gustafsson, Stefan, Bartz, Traci M., Bellenguez, Céline, Vidal, Jean Sebastien, Jian, Xueqiu, Kjartansson, Olafur, Wiggins, Kerri L., Satizabal, Claudia L., Xue, Flora, Ripatti, Samuli, Liu, Yongmei, Deelen, Joris, den Hoed, Marcel, Bevan, Steve, Hopewell, Jemma C., Malik, Rainer, Heckbert, Susan R., Rice, Kenneth, Smith, Nicholas L., Levi, Christopher, Sharma, Pankaj, Sudlow, Cathie LM, Nik, Ali Moussavi, Cole, John W., Schmidt, Reinhold, Meschia, James, Thijs, Vincent, Lindgren, Arne, Melander, Olle, Grewal, Raji P., Sacco, Ralph L., Rundek, Tatjana, Rothwell, Peter M., Arnett, Donna K., Jern, Christina, Johnson, Julie A., Benavente, Oscar R., Wassertheil-Smoller, Sylvia, Lee, Jin-Moo, Wong, Quenna, Aparicio, Hugo J., Engelter, Stefan T., Kloss, Manja, Leys, Didier, Pezzini, Alessandro, Buring, Julie E., Ridker, Paul M., Berr, Claudine, Dartigues, Jean-François, Hamsten, Anders, Magnusson, Patrik K., Traylor, Matthew, Pedersen, Nancy L., Lannfelt, Lars, Lindgren, Lars, Lindgren, Cecilia M., Morris, Andrew P., Jimenez-Conde, Jordi, Montaner, Joan, Radmanesh, Farid, Slowik, Agnieszka, Woo, Daniel, Hofman, Albert, Koudstaal, Peter J., Portegies, Marileen L. P., Uitterlinden, André G., de Craen, Anton J. M., Ford, Ian, Jukema, J. Wouter, Stott, David J., Allen, Norrina B., Sale, Michele M., Johnson, Andrew D., Bennett, David A., De Jager, Philip L., White, Charles C., Grabe, Hans Jörgen, Markus, Marcello Ricardo Paulista, Schminke, Ulf, Boncoraglio, Giorgio B., Clarke, Robert, Kamatani, Yoichiro, Dallongeville, Jean, Lopez, Oscar L., Rotter, Jerome I., Nalls, Michael A., Gottesman, Rebecca F., Griswold, Michael E., Knopman, David S., Windham, B. Gwen, Beiser, Alexa, Markus, Hugh S., Vartiainen, Erkki, French, Curtis R., Dichgans, Martin, Pastinen, Tomi, Lathrop, Mark, Gudnason, Vilmundur, Kurth, Tobias, Psaty, Bruce M., Harris, Tamara B., Rich, Stephen S., deStefano, Anita L., Schmidt, Carsten Oliver, Worrall, Bradford B., Rosand, Jonathan, Salomaa, Veikko, Mosley, Thomas H., Ingelsson, Erik, van Duijn, Cornelia M., Tzourio, Christophe, Rexrode, Kathryn M., Lehmann, Ordan J., Launer, Lenore J., Ikram, M. Arfan, Carlsson, Peter, Chasman, Daniel I., Childs, Sarah J., Longstreth, William T., Seshadri, Sudha, and Debette, Stéphanie
- Abstract
BACKGROUND: Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. METHODS: For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p<5 × 10(-6)) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-wide significant findings (at p<5 × 10(-8)), we explored associations with additional cerebrovascular phenotypes and did functional experiments using conditional (inducible) deletion of the probable causal gene in mice. We also studied the expression of orthologs of this probable causal gene and its effects on cerebral vasculature in zebrafish mutants. FINDINGS: We replicated seven of eight known loci associated with risk for ischaemic stroke, and identified a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with risk of all-stroke (odds ratio [OR] 1·08, 95% CI 1·05-1·12, p=1·48 × 10(-8); minor allele frequency 21%). The rs12204590 stroke risk allele was also associated with increased MRI-defined burden of white matter hyperintensity-a marker of cerebral small vessel dise
9. Extracellular cathepsin Z signals through the α5 integrin and augments NLRP3 inflammasome activation.
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Campden, Rhiannon I., Warren, Amy L., Greene, Catherine J., Chiriboga, Jose A., Arnold, Corey R., Aggarwal, Devin, McKenna, Neil, Sandall, Christina F., MacDonald, Justin A., and Yates, Robin M.
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NLRP3 protein , *INFLAMMASOMES , *ENZYME-linked immunosorbent assay , *OCCUPATIONAL diseases , *DENDRITIC cells , *ELASTASES , *INTEGRINS - Abstract
Respiratory silicosis is a preventable occupational disease that develops secondary to the aspiration of crystalline silicon dioxide (silica) into the lungs, activation of the NLRP3 inflammasome, and IL-1β production. Cathepsin Z has been associated with the development of inflammation and IL-1β production; however, the mechanism of how cathepsin Z leads to IL-1β production is unknown. Here, the requirement for cathepsin Z in silicosis was determined using WT mice and mice deficient in cathepsin Z. The activation of the NLRP3 inflammasome in macrophages was studied using WT and cathepsin Z-deficient bone marrow-derived murine dendritic cells and the human monocytic cell line THP-1. The cells were activated with silica, and IL-1β release was determined using enzyme-linked immunosorbent assay or IL-1β bioassays. The relative contribution of the active domain or integrin-binding domain of cathepsin Z was studied using recombinant cathepsin Z constructs and the α5 integrin neutralizing antibody. We report that the lysosomal cysteine protease cathepsin Z potentiates the development of inflammation associated with respiratory silicosis by augmenting NLRP3 inflammasome-derived IL-1β expression in response to silica. The secreted cathepsin Z functions nonproteolytically via the internal integrin-binding domain to impact caspase-1 activation and the production of active IL-1β through integrin α5 without affecting the transcription levels of NLRP3 inflammasome components. This work reveals a regulatory pathway for the NLRP3 inflammasome that occurs in an outside-in fashion and provides a link between extracellular cathepsin Z and inflammation. Furthermore, it reveals a level of NLRP3 inflammasome regulation that has previously only been found downstream of extracellular pathogens. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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10. Cohort profile: investigating SARS-CoV-2 infection and the health and psychosocial impact of the COVID-19 pandemic in the Canadian CHILD Cohort.
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Azeez R, Lotoski L, Dubeau A, Rodriguez N, Reyna ME, Freitas T, Goguen S, Medeleanu M, Winsor GL, Brinkman FSL, Cameron EE, Roos L, Simons E, Moraes TJ, Mandhane PJ, Turvey SE, Bolotin S, Wright K, McNeil D, Patrick DM, Bullard J, Langlois MA, Arnold CR, Galipeau Y, Pelchat M, Doucas N, Subbarao P, and Azad MB
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- Adult, Humans, Canada epidemiology, Cohort Studies, Pandemics, Prospective Studies, SARS-CoV-2, COVID-19 epidemiology, COVID-19 psychology, Psychological Distress
- Abstract
The coronavirus disease 2019 (COVID-19) pandemic has affected all Canadian families, with some impacted differently than others. Our study aims to: (1) determine the prevalence and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Canadian families, (2) identify predictors of infection susceptibility and severity of SARS-CoV-2, and (3) identify health and psychosocial impacts of the COVID-19 pandemic. This study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3,454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009 and 2012. During the pandemic, CHILD households were invited to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure and testing, vaccination status, physical and mental health, and pandemic-driven life changes; and (3) in-home biological sampling kits to collect blood and stool. In total, 1,462 households (5,378 participants) consented to the CHILD COVID-19 Add-On Study: 2,803 children (mean±standard deviation [SD], 9.0±2.7 years; range, 0-17 years) and 2,576 adults (mean±SD, 43.0±6.5 years; range, 18-85 years). We will leverage the wealth of pre-pandemic CHILD data to identify risk and resilience factors for susceptibility and severity to the direct and indirect pandemic effects. Our short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.
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- 2023
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11. Extracellular cathepsin Z signals through the α 5 integrin and augments NLRP3 inflammasome activation.
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Campden RI, Warren AL, Greene CJ, Chiriboga JA, Arnold CR, Aggarwal D, McKenna N, Sandall CF, MacDonald JA, and Yates RM
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- Animals, Inflammation metabolism, Integrin alpha5 metabolism, Interleukin-1beta metabolism, Mice, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Silicon Dioxide pharmacology, Silicosis metabolism, Cathepsin Z metabolism, Inflammasomes metabolism
- Abstract
Respiratory silicosis is a preventable occupational disease that develops secondary to the aspiration of crystalline silicon dioxide (silica) into the lungs, activation of the NLRP3 inflammasome, and IL-1β production. Cathepsin Z has been associated with the development of inflammation and IL-1β production; however, the mechanism of how cathepsin Z leads to IL-1β production is unknown. Here, the requirement for cathepsin Z in silicosis was determined using WT mice and mice deficient in cathepsin Z. The activation of the NLRP3 inflammasome in macrophages was studied using WT and cathepsin Z-deficient bone marrow-derived murine dendritic cells and the human monocytic cell line THP-1. The cells were activated with silica, and IL-1β release was determined using enzyme-linked immunosorbent assay or IL-1β bioassays. The relative contribution of the active domain or integrin-binding domain of cathepsin Z was studied using recombinant cathepsin Z constructs and the α
5 integrin neutralizing antibody. We report that the lysosomal cysteine protease cathepsin Z potentiates the development of inflammation associated with respiratory silicosis by augmenting NLRP3 inflammasome-derived IL-1β expression in response to silica. The secreted cathepsin Z functions nonproteolytically via the internal integrin-binding domain to impact caspase-1 activation and the production of active IL-1β through integrin α5 without affecting the transcription levels of NLRP3 inflammasome components. This work reveals a regulatory pathway for the NLRP3 inflammasome that occurs in an outside-in fashion and provides a link between extracellular cathepsin Z and inflammation. Furthermore, it reveals a level of NLRP3 inflammasome regulation that has previously only been found downstream of extracellular pathogens., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
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