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1. Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures

Author

Sluka, Kathleen A, Wager, Tor D, Sutherland, Stephani P, Labosky, Patricia A, Balach, Tessa, Bayman, Emine O, Berardi, Giovanni, Brummett, Chad M, Burns, John, Buvanendran, Asokumar, Caffo, Brian, Calhoun, Vince D, Clauw, Daniel, Chang, Andrew, Coffey, Christopher S, Dailey, Dana L, Ecklund, Dixie, Fiehn, Oliver, Fisch, Kathleen M, Law, Laura A Frey, Harris, Richard E, Harte, Steven E, Howard, Timothy D, Jacobs, Joshua, Jacobs, Jon M, Jepsen, Kristen, Johnston, Nicolas, Langefeld, Carl D, Laurent, Louise C, Lenzi, Rebecca, Lindquist, Martin A, Lokshin, Anna, Kahn, Ari, McCarthy, Robert J, Olivier, Michael, Porter, Linda, Qian, Wei-Jun, Sankar, Cheryse A, Satterlee, John, Swensen, Adam C, Vance, Carol GT, Waljee, Jennifer, Wandner, Laura D, Williams, David A, Wixson, Richard L, Zhou, Xiaohong Joe, and Consortium, the A2CPS

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Precision Medicine, Pain Research, Biotechnology, Clinical Research, Behavioral and Social Science, Chronic Pain, Prevention, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, Proteomics, Pain, Postoperative, Acute Pain, Biomarkers, Pain, Chronic pain, Postsurgical pain, Biomarker, Biosignatures, Omics, Brain imaging, Psychosocial, A2CPS Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Anesthesiology, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

AbstractChronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Published
2023

2. Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function

Author

Zhang, Yuankai, Liu, Xue, Wiggins, Kerri L, Kurniansyah, Nuzulul, Guo, Xiuqing, Rodrigue, Amanda L, Zhao, Wei, Yanek, Lisa R, Ratliff, Scott M, Pitsillides, Achilleas, Aguirre Patiño, Juan Sebastian, Sofer, Tamar, Arking, Dan E, Austin, Thomas R, Beiser, Alexa S, Blangero, John, Boerwinkle, Eric, Bressler, Jan, Curran, Joanne E, Hou, Lifang, Hughes, Timothy M, Kardia, Sharon LR, Launer, Lenore J, Levy, Daniel, Mosley, Thomas H, Nasrallah, Ilya M, Rich, Stephen S, Rotter, Jerome I, Seshadri, Sudha, Tarraf, Wassim, González, Kevin A, Ramachandran, Vasan, Yaffe, Kristine, Nyquist, Paul A, Psaty, Bruce M, DeCarli, Charles S, Smith, Jennifer A, Glahn, David C, González, Hector M, Bis, Joshua C, Fornage, Myriam, Heckbert, Susan R, Fitzpatrick, Annette L, Liu, Chunyu, Satizabal, Claudia L, Aguilera, Norma, Ament, Seth, Ammous, Farah, Arnett, Donna K, Becker, Diane, Bis, Joshua, Blue, Elizabeth, Breaux, Camille, Chaar, Dima, MHI, Clarkson-Townsend, Danielle, Cooper, Brigidann, Coresh, Josef, Correa, Adolfo, DeStefano, Anita, Ding, Jingzhong, Fardo, David, Fitzpatrick, Annette, French, Jennifer, Glahn, David, Gonzalez, Hector, Granot-Hershkovitz, Einat, Hanly, Patrick, Hayden, Kathleen, Heckbert, Susan, Heemann, Scott, Horvath, Steve, Hoth, Karin, Hughes, Timothy, Jaiswal, Sidd, Jian, Xueqiu, Katsumata, Yuriko, Kho, Minjung, Kooperberg, Charles, Launer, Lenore, Lin, Honghuang, Litkowski, Elizabeth, Longstreth, Will, Martin, Alexandra, Mayeux, Richard, Mikulla, Julie, Miller, Amy, Misra, Biswapriya, Mosley, Thomas, Nyquist, Paul, O'Connell, Jeff, Olivier, Michael, Peloso, Gina, Perry, James, Psaty, Bruce, Purcell, Shaun, and Raffield, Laura

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Acquired Cognitive Impairment, Neurodegenerative, Precision Medicine, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biomedical Imaging, Alzheimer's Disease, Clinical Research, Dementia, Behavioral and Social Science, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Neurological, Mental health, Good Health and Well Being, Middle Aged, Humans, Female, Aged, Male, DNA, Mitochondrial, DNA Copy Number Variations, Prospective Studies, Cross-Sectional Studies, Alzheimer Disease, Magnetic Resonance Imaging, Cognition, Brain, NHLBI Trans-Omics for Precision Medicine (TOPMed) program, Mitochondrial and Neurocognitive Working Groups, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

Background and objectivesPrevious studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.MethodsWe included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear DNA. Brain MRI markers included total brain, hippocampal, and white matter hyperintensity volumes. General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5-20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (

Published
2023

3. Nitrous Oxide Manifold and Other Reduction of Emissions (NoMoreGas): a multicentre observational study evaluating pre-utilisation loss of nitrous oxide

Author

Baker, Chloe, Begum, Farzana, Brown, Elizabeth, Eshelby, Sarah, Flower, Luke, Fullbrook, Aidan, Greenshields, Nicole, Lignos, Leda, May, Shaun, Meeks, Daveena, Milne, Benjamin, Murali, Mayur, Nolan, Louise, Oddy, Chris, Patel, Mitul, Rhodes, Kimberley, Sadeghi, Abtin, Samways, Adam, Sanganee, Urvi, Shah, Shilen, Tian, Sarah, Ahmed, Arif, Amaradasa, Natasha, Baillie, Hamish, Baily, Duncan, Bandopadhyay, Rahul, Berg, Jen, Bhugra, Nikita, Bloomfield, Sophie, Braude, David, Chong, Mickey, Dabrowicz, Adrian, Desouza, Christopher, Eltaher, Mustafa, Evans, Emma, Feben, Alex, Gadepalli, Aditya, Gallop, Felicity, Gheith, Mohamed, Graham, Chris, Haas-Heger, Tabea, Hall, Chloe, Hall, Thomas, Kale, Snehal, Khaleeq, Sophia, Koirala, Aashish, Kovac, Maja, Lanka, Anupama, Li, Alison, Macleod, Cameron, Mammen, Sowmia, Mansoubi, Vafa, Morillon, Paul, Morley, Olivia, Morrison, Hannah, Nawaz, Tooba, Ng, Winston, Olivier, Michael, Partridge, Lucy, Patel, Anesh, Patel, Shriyam, Pearcey, Leon, Petrescu, Ruxandra, Powell, Emily, Mohammed, Rageh, Rahman, Aktar, Redington, Katie, Ruck, Claire, Saviani, Michela, Schofield, Sophie, Sharieff, Imran, Shields, Natalie, Singh, Ariana, Sithirangathan, Suzzan, Stead, Richard, Tan, Andrew, Thompson, Oliver, Tomlin, Rachael, Vaghela, Madhvi, Vaidya, Shriram, Vakil, Bhavya, Van Ross, Jen, Venkitaramanan, Arun, Wickramasuriya, Thilini, Wicks, Georgie, Wijesinghe, Indeewarie, Yearwood, Alice, Thomas, Megan A.F., Ward, Christopher J., Sinnott, Matthew E., Davies, Thomas W., Wong, Jan M., Wong, Joanna K.L., Kunst, Gudrun, and Anwar, Sibtain

Published
2024
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4. Multi-Site Observational Study to Assess Biomarkers for Susceptibility or Resilience to Chronic Pain: The Acute to Chronic Pain Signatures (A2CPS) Study Protocol

Author

Berardi, Giovanni, Frey-Law, Laura, Sluka, Kathleen A, Bayman, Emine O, Coffey, Christopher S, Ecklund, Dixie, Vance, Carol GT, Dailey, Dana L, Burns, John, Buvanendran, Asokumar, McCarthy, Robert J, Jacobs, Joshua, Zhou, Xiaohong Joe, Wixson, Richard, Balach, Tessa, Brummett, Chad M, Clauw, Daniel, Colquhoun, Douglas, Harte, Steven E, Harris, Richard E, Williams, David A, Chang, Andrew C, Waljee, Jennifer, Fisch, Kathleen M, Jepsen, Kristen, Laurent, Louise C, Olivier, Michael, Langefeld, Carl D, Howard, Timothy D, Fiehn, Oliver, Jacobs, Jon M, Dakup, Panshak, Qian, Wei-Jun, Swensen, Adam C, Lokshin, Anna, Lindquist, Martin, Caffo, Brian S, Crainiceanu, Ciprian, Zeger, Scott, Kahn, Ari, Wager, Tor, Taub, Margaret, Ford, James, Sutherland, Stephani P, and Wandner, Laura D

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Pain Research, Prevention, Chronic Pain, Clinical Research, Neurological, Musculoskeletal, Good Health and Well Being, postsurgical pain, thoracic surgery, pain, biomarker, risk factors, protocol, knee arthroplasty, Biomedical and clinical sciences, Health sciences
Abstract

Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic Pain Signatures (A2CPS) Program aims to characterize the predictive nature of biomarkers (brain imaging, high-throughput molecular screening techniques, or "omics," quantitative sensory testing, patient-reported outcome assessments and functional assessments) to identify individuals who will develop chronic pain following surgical intervention. The A2CPS is a multisite observational study investigating biomarkers and collective biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain following knee arthroplasty and thoracic surgery. This manuscript provides an overview of data collection methods and procedures designed to standardize data collection across multiple clinical sites and institutions. Pain-related biomarkers are evaluated before surgery and up to 3 months after surgery for use as predictors of patient reported outcomes 6 months after surgery. The dataset from this prospective observational study will be available for researchers internal and external to the A2CPS Consortium to advance understanding of the transition from acute to chronic postsurgical pain.

Published
2022

9. Whole genome sequence analyses of brain imaging measures in the Framingham Study

Author

Sarnowski, Chloé, Satizabal, Claudia L, DeCarli, Charles, Pitsillides, Achilleas N, Cupples, L Adrienne, Vasan, Ramachandran S, Wilson, James G, Bis, Joshua C, Fornage, Myriam, Beiser, Alexa S, DeStefano, Anita L, Dupuis, Josée, Seshadri, Sudha, Arnett, Donna K, Becker, Diane, Bis, Joshua, Boerwinkle, Eric, Bowers, Michael, Bressler, Jan, Correa, Adolfo, DeStefano, Anita, Ding, Jingzhong ding, Fardo, David, Lugo, Alex Garcia, Glahn, David, Gonzalez, Hector, Hayden, Kathleen, Heckbert, Susan, Hoth, Karin, Hughes, Timothy, Jaquish, Cashell, Jian, Xueqiu, Knowles, Emma, Launer, Lenore, Lin, Honghuang, Longstreth, Will, Mayeux, Richard, Misra, Biswapriya, Mosley, Thomas, Nyquist, Paul, Olivier, Michael, Peprah, Emmanuel, Psaty, Bruce, Purcell, Shaun, Rotter, Jerome, Satizabal, Claudia, Schellenberg, Gerard, Simino, Jeannette, Smith, Jennifer, Smoller, Sylvia, Snively, Beverly, Sokolow, Sophie, Wehr, Kate, Yanek, Lisa, Yang, Qiong, Namiko, Abe, Goncalo, Abecasis, Christine, Albert, Nicholette (Nichole) Palmer, Allred, Laura, Almasy, Alvaro, Alonso, Seth, Ament, Peter, Anderson, Pramod, Anugu, Deborah, Applebaum-Bowden, Dan, Arking, Donna K, Arnett, Allison, Ashley-Koch, Stella, Aslibekyan, Tim, Assimes, Paul, Auer, Dimitrios, Avramopoulos, John, Barnard, Kathleen, Barnes, Graham, Barr R, Emily, Barron-Casella, Terri, Beaty, Diane, Becker, Lewis, Becker, Rebecca, Beer, Ferdouse, Begum, Amber, Beitelshees, Emelia, Benjamin, Marcos, Bezerra, Larry, Bielak, Joshua, Bis, Thomas, Blackwell, John, Blangero, Eric, Boerwinkle, Ingrid, Borecki, Russell, Bowler, Jennifer, Brody, Ulrich, Broeckel, Jai, Broome, Karen, Bunting, Esteban, Burchard, and Jonathan, Cardwell

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Human Genome, Brain Disorders, Neurodegenerative, Biotechnology, Clinical Research, Aging, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Aged, Brain, Female, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Massachusetts, Middle Aged, Organ Size, Phenotype, Prospective Studies, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Neurocognitive Working Group, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program.MethodsWe performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants.ResultsWe detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10-8) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10-8). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10-4) and in 17q25 for WMH (rs7214628, p = 2.0 × 10-3) were confirmed. Gene-based tests detected associations (p ≤ 2.3 × 10-6) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- (UNC5D) and Parkinson disease-associated genes (GBA). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways.ConclusionsWhole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings.

Published
2018

10. Cardiac Molecular Analysis Reveals Aging‐Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation via Hexosamine Biosynthetic Pathway.

Author

Grilo, Luís F., Zimmerman, Kip D., Puppala, Sobha, Chan, Jeannie, Huber, Hillary F., Li, Ge, Jadhav, Avinash Y. L., Wang, Benlian, Li, Cun, Clarke, Geoffrey D., Register, Thomas C., Oliveira, Paulo J., Nathanielsz, Peter W., Olivier, Michael, Pereira, Susana P., and Cox, Laura A.

Subjects
KREBS cycle, CARDIAC hypertrophy, HEART metabolism, DISEASE risk factors, AGE, GLYCOSAMINOGLYCANS
Abstract

Age is a prominent risk factor for cardiometabolic disease, often leading to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling and dysfunction exclusively resulting from physiological aging remain elusive. Previous research demonstrated age‐related functional alterations in baboons, analogous to humans. The goal of this study is to identify early cardiac molecular alterations preceding functional adaptations, shedding light on the regulation of age‐associated changes. Unbiased transcriptomics of left ventricle samples are performed from female baboons aged 7.5–22.1 years (human equivalent ≈30–88 years). Weighted‐gene correlation network and pathway enrichment analyses are performed, with histological validation. Modules of transcripts negatively correlated with age implicated declined metabolism‐oxidative phosphorylation, tricarboxylic acid cycle, glycolysis, and fatty‐acid β‐oxidation. Transcripts positively correlated with age suggested a metabolic shift toward glucose‐dependent anabolic pathways, including hexosamine biosynthetic pathway (HBP). This shift is associated with increased glycosaminoglycan synthesis, modification, precursor synthesis via HBP, and extracellular matrix accumulation, verified histologically. Upregulated extracellular matrix‐induced signaling coincided with glycosaminoglycan accumulation, followed by cardiac hypertrophy‐related pathways. Overall, these findings revealed a transcriptional shift in metabolism favoring glycosaminoglycan accumulation through HBP before cardiac hypertrophy. Unveiling this metabolic shift provides potential targets for age‐related cardiac diseases, offering novel insights into early age‐related mechanisms. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation

Author

Chu, Audrey Y, Deng, Xuan, Fisher, Virginia A, Drong, Alexander, Zhang, Yang, Feitosa, Mary F, Liu, Ching-Ti, Weeks, Olivia, Choh, Audrey C, Duan, Qing, Dyer, Thomas D, Eicher, John D, Guo, Xiuqing, Heard-Costa, Nancy L, Kacprowski, Tim, Kent, Jack W, Lange, Leslie A, Liu, Xinggang, Lohman, Kurt, Lu, Lingyi, Mahajan, Anubha, O'Connell, Jeffrey R, Parihar, Ankita, Peralta, Juan M, Smith, Albert V, Zhang, Yi, Homuth, Georg, Kissebah, Ahmed H, Kullberg, Joel, Laqua, René, Launer, Lenore J, Nauck, Matthias, Olivier, Michael, Peyser, Patricia A, Terry, James G, Wojczynski, Mary K, Yao, Jie, Bielak, Lawrence F, Blangero, John, Borecki, Ingrid B, Bowden, Donald W, Carr, John Jeffrey, Czerwinski, Stefan A, Ding, Jingzhong, Friedrich, Nele, Gudnason, Vilmunder, Harris, Tamara B, Ingelsson, Erik, Johnson, Andrew D, Kardia, Sharon LR, Langefeld, Carl D, Lind, Lars, Liu, Yongmei, Mitchell, Braxton D, Morris, Andrew P, Mosley, Thomas H, Rotter, Jerome I, Shuldiner, Alan R, Towne, Bradford, Völzke, Henry, Wallaschofski, Henri, Wilson, James G, Allison, Matthew, Lindgren, Cecilia M, Goessling, Wolfram, Cupples, L Adrienne, Steinhauser, Matthew L, and Fox, Caroline S

Subjects
Biological Sciences, Genetics, Prevention, Human Genome, Adipocytes, Animals, Body Fat Distribution, Cell Differentiation, Cohort Studies, Ethnicity, Female, Genetic Loci, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mice, Mice, Inbred C57BL, Obesity, Phenotype, Polymorphism, Single Nucleotide, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10-8; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

Published
2017

15. Tumour-specific amplitude-modulated radiofrequency electromagnetic fields induce differentiation of hepatocellular carcinoma via targeting Cav3.2 T-type voltage-gated calcium channels and Ca2+ influx

Author

Jimenez, Hugo, Wang, Minghui, Zimmerman, Jacquelyn W., Pennison, Michael J., Sharma, Sambad, Surratt, Trevor, Xu, Zhi-Xiang, Brezovich, Ivan, Absher, Devin, Myers, Richard M., DeYoung, Barry, Caudell, David L., Chen, Dongquan, Lo, Hui-Wen, Lin, Hui-Kuan, Godwin, Dwayne W., Olivier, Michael, Ghanekar, Anand, Chen, Kui, Miller, Lance D., Gong, Yijian, Capstick, Myles, D'Agostino, Ralph B., Jr, Munden, Reginald, Merle, Philippe, Barbault, Alexandre, Blackstock, Arthur W., Bonkovsky, Herbert L., Yang, Guang-Yu, Jin, Guangxu, Liu, Liang, Zhang, Wei, Watabe, Kounosuke, Blackman, Carl F., and Pasche, Boris C.

Published
2019
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18. Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation Via Hexosamine Biosynthetic Pathway

Author

Grilo, Luís F., primary, Zimmerman, Kip D., additional, Puppala, Sobha, additional, Chan, Jeannie, additional, Huber, Hillary F., additional, Li, Ge, additional, Jadhav, Avinash Y. L., additional, Wang, Benlian, additional, Li, Cun, additional, Clarke, Geoffrey D., additional, Register, Thomas C., additional, Oliveira, Paulo J., additional, Nathanielsz, Peter W., additional, Olivier, Michael, additional, Pereira, Susana P., additional, and Cox, Laura A., additional

Published
2023
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19. Genetic Variation in Aldosterone Synthase Predicts Plasma Glucose Levels

Author

Ranade, Koustubh, Wu, Kwan Dun, Risch, Neil, Olivier, Michael, Pei, Dee, Hsiao, Chin-Fu, Chuang, Lee-Ming, Ho, Low-Tone, Jorgenson, Eric, Pesich, Robert, Chen, Yii-Der I., Dzau, Victor, Lin, Alfred, Olshen, Richard A., Curb, David, Cox, David R., and Botstein, David

Published
2001

21. A High-Resolution Radiation Hybrid Map of the Human Genome Draft Sequence

Author

Olivier, Michael, Aggarwal, Amita, Allen, Jennifer, Almendras, Annalisa A., Bajorek, Eva S., Beasley, Ellen M., Brady, Shannon D., Bushard, Jannette M., Bustos, Valerie I., Chu, Angela, Chung, Tisha R., de Witte, Anniek, Denys, Mirian E., Dominguez, Rakly, Fang, Nicole Y., Foster, Brian D., Freudenberg, Robert W., Hadley, David, Hamilton, Libby R., Jeffrey, Tonya J., Kelly, Libusha, Lazzeroni, Laura, Levy, Michelle R., Lewis, Saskia C., Liu, Xia, Lopez, Frederick J., Louie, Brent, Marquis, Joseph P., Martinez, Robert A., Matsuura, Margaret K., Misherghi, Nedda S., Norton, Jolanna A., Olshen, Adam, Perkins, Shanti M., Perou, Amy J., Piercy, Chris, Piercy, Mark, Qin, Fawn, Reif, Tim, Sheppard, Kelly, Shokoohi, Vida, Smick, Geoff A., Sun, Wei-Lin, Stewart, Elizabeth A., Tejeda, J. Fernando, Tran, Nguyet M., Trejo, Tonatiuh, Vo, Nu T., Zierten, Deborah L., Zhao, Shaying, Sachidanandam, Ravi, Trask, Barbara J., Myers, Richard M., and Cox, David R.

Published
2001

22. Linkage and association of haplotypes at the APOA1/C3/A4/A5 gene cluster to familial combined hyperlipidemia

Author

Eichenbaum-Voline, Sophie, Olivier, Michael, Jones, Emma L., Naoumova, Rossitza P., Jones, Bethan, Gau, Brian, Seed, Mary, Betteridge, D. John, Galton, David J., Rubin, Edward M., Scott, James, Shoulders, Carol C., and Pennacchio, Len A.

Subjects
Basic biological sciences
Abstract

Combined hyperlipidemia (CHL) is a common disorder of lipid metabolism that leads to an increased risk of cardiovascular disease. The lipid profile of CHL is characterised by high levels of atherogenic lipoproteins and low levels of high-density-lipoprotein-cholesterol. Apolipoprotein (APO) A5 is a newly discovered gene involved in lipid metabolism located within 30kbp of the APOA1/C3/A4 gene cluster. Previous studies have indicated that sequence variants in this cluster are associated with increased plasma lipid levels. To establish whether variation at the APOA5 gene contributes to the transmission of CHL, we performed linkage and linkage disequilibrium (LD) tests on a large cohort of families (n=128) with familial CHL (FCHL). The linkage data produced evidence for linkage of the APOA1/C3/A4/A5 genomic interval to FCHL (NPL = 1.7, P = 0.042). The LD studies substantiated these data. Two independent rare alleles, APOA5c.56G and APOC3c.386G of this gene cluster were over-transmitted in FCHL (P = 0.004 and 0.007, respectively), and this was associated with a reduced transmission of the most common APOA1/C3/A4/A5 haplotype (frequency 0.4425) to affected subjects (P = 0.013). The APOA5c.56G allele was associated with increased plasma triglyceride levels in FCHL probands, whereas the second, and independent, APOC3c.386G allele was associated with increased plasma triglyceride levels in FCHL pedigree founders. Thus, this allele (or an allele in LD) may mark a quantitative trait associated with FCHL, as well as representing a disease susceptibility locus for the condition. This study establishes that sequence variation in the APOA1/C3/A4/A5 gene cluster contributes to the transmission of FCHL in a substantial proportion of affected families, and that these sequence variants may also contribute to the lipid abnormalities of the metabolic syndrome, which is present in up to 40 percent of persons with cardiovascular disease.

Published
2002

23. Multi-omics Analysis of Aging Liver Reveals Changes in Endoplasmic Stress and Degradation Pathways in Female Nonhuman Primates

Author

Puppala, Sobha, primary, Chan, Jeannie, additional, Zimmerman, Kip D, additional, Hamid, Zeeshan, additional, Ampong, Isaac, additional, Huber, Hillary F, additional, Li, Ge, additional, Jadhav, Avinash Y.L., additional, Li, Cun, additional, Nathanielsz, Peter W., additional, Olivier, Michael, additional, and Cox, Laura A., additional

Published
2023
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25. HyCCAPP as a tool to characterize promoter DNA-protein interactions in Saccharomyces cerevisiae

Author

Guillen-Ahlers, Hector, Rao, Prahlad K., Levenstein, Mark E., Kennedy-Darling, Julia, Perumalla, Danu S., Jadhav, Avinash Y.L., Glenn, Jeremy P., Ludwig-Kubinski, Amy, Drigalenko, Eugene, Montoya, Maria J., Göring, Harald H., Anderson, Corianna D., Scalf, Mark, Gildersleeve, Heidi I.S., Cole, Regina, Greene, Alexandra M., Oduro, Akua K., Lazarova, Katarina, Cesnik, Anthony J., Barfknecht, Jared, Cirillo, Lisa A., Gasch, Audrey P., Shortreed, Michael R., Smith, Lloyd M., and Olivier, Michael

Published
2016
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26. Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures.

Author

Sluka, Kathleen, Sluka, Kathleen, Wager, Tor, Sutherland, Stephani, Labosky, Patricia, Balach, Tessa, Bayman, Emine, Berardi, Giovanni, Brummett, Chad, Burns, John, Buvanendran, Asokumar, Caffo, Brian, Calhoun, Vince, Clauw, Daniel, Chang, Andrew, Coffey, Christopher, Dailey, Dana, Ecklund, Dixie, Fisch, Kathleen, Frey Law, Laura, Harris, Richard, Harte, Steven, Howard, Timothy, Jacobs, Joshua, Jacobs, Jon, Jepsen, Kristen, Johnston, Nicolas, Langefeld, Carl, Laurent, Louise, Lenzi, Rebecca, Lindquist, Martin, Lokshin, Anna, Kahn, Ari, McCarthy, Robert, Olivier, Michael, Porter, Linda, Qian, Wei-Jun, Sankar, Cheryse, Satterlee, John, Swensen, Adam, Vance, Carol, Waljee, Jennifer, Wandner, Laura, Williams, David, Wixson, Richard, Zhou, Xiaohong, Fiehn, Oliver, Sluka, Kathleen, Sluka, Kathleen, Wager, Tor, Sutherland, Stephani, Labosky, Patricia, Balach, Tessa, Bayman, Emine, Berardi, Giovanni, Brummett, Chad, Burns, John, Buvanendran, Asokumar, Caffo, Brian, Calhoun, Vince, Clauw, Daniel, Chang, Andrew, Coffey, Christopher, Dailey, Dana, Ecklund, Dixie, Fisch, Kathleen, Frey Law, Laura, Harris, Richard, Harte, Steven, Howard, Timothy, Jacobs, Joshua, Jacobs, Jon, Jepsen, Kristen, Johnston, Nicolas, Langefeld, Carl, Laurent, Louise, Lenzi, Rebecca, Lindquist, Martin, Lokshin, Anna, Kahn, Ari, McCarthy, Robert, Olivier, Michael, Porter, Linda, Qian, Wei-Jun, Sankar, Cheryse, Satterlee, John, Swensen, Adam, Vance, Carol, Waljee, Jennifer, Wandner, Laura, Williams, David, Wixson, Richard, Zhou, Xiaohong, and Fiehn, Oliver

Abstract

Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPSs initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Published
2023

34. Integrated Multi-Omics Analysis of Brain Aging in Female Nonhuman Primates Reveals Altered Signaling Pathways Relevant to Age-Related Disorders

Author

Cox, Laura A., primary, Puppala, Sobha, additional, Chan, Jeannie, additional, Zimmerman, Kip D., additional, Hamid, Zeeshan, additional, Ampong, Isaac, additional, Huber, Hillary F., additional, Li, Ge, additional, Jadhav, Avinash Y. L., additional, Wang, Benlian, additional, Li, Cun, additional, Shively, Carol, additional, Clarke, Geoffrey D., additional, Register, Thomas C., additional, Nathanielsz, Peter W., additional, and Olivier, Michael, additional

Published
2022
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39. Multi-Site Observational Study to Assess Biomarkers for Susceptibility or Resilience to Chronic Pain: The Acute to Chronic Pain Signatures (A2CPS) Study Protocol

Author

Berardi, Giovanni, primary, Frey-Law, Laura, additional, Sluka, Kathleen A., additional, Bayman, Emine O., additional, Coffey, Christopher S., additional, Ecklund, Dixie, additional, Vance, Carol G. T., additional, Dailey, Dana L., additional, Burns, John, additional, Buvanendran, Asokumar, additional, McCarthy, Robert J., additional, Jacobs, Joshua, additional, Zhou, Xiaohong Joe, additional, Wixson, Richard, additional, Balach, Tessa, additional, Brummett, Chad M., additional, Clauw, Daniel, additional, Colquhoun, Douglas, additional, Harte, Steven E., additional, Harris, Richard E., additional, Williams, David A., additional, Chang, Andrew C., additional, Waljee, Jennifer, additional, Fisch, Kathleen M., additional, Jepsen, Kristen, additional, Laurent, Louise C., additional, Olivier, Michael, additional, Langefeld, Carl D., additional, Howard, Timothy D., additional, Fiehn, Oliver, additional, Jacobs, Jon M., additional, Dakup, Panshak, additional, Qian, Wei-Jun, additional, Swensen, Adam C., additional, Lokshin, Anna, additional, Lindquist, Martin, additional, Caffo, Brian S., additional, Crainiceanu, Ciprian, additional, Zeger, Scott, additional, Kahn, Ari, additional, Wager, Tor, additional, Taub, Margaret, additional, Ford, James, additional, Sutherland, Stephani P., additional, and Wandner, Laura D., additional

Published
2022
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41. Additional file 4 of Assessment of label-free quantification and missing value imputation for proteomics in non-human primates

Author

Hamid, Zeeshan, Zimmerman, Kip D., Guillen-Ahlers, Hector, Li, Cun, Nathanielsz, Peter, Cox, Laura A., and Olivier, Michael

Subjects
nervous system
Abstract

Additional file 4: Supp. File 4. Sequence coverage of reference protein carbonic anhydrase 3 (CA3) observed in our study and MS/MS spectral match of various PTMs identified for reference peptide from CA3. Additional information of co-eluting peptides is also included.

Published
2022
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42. FILTER FRESH

Author

Olivier, Michael and Dalton, David

Published
2002

46. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations

Author

Hayes, M. Geoffrey, Urbanek, Margrit, Ehrmann, David A., Armstrong, Loren L., Lee, Ji Young, Sisk, Ryan, Karaderi, Tugce, Barber, Thomas M., McCarthy, Mark I., Franks, Stephen, Lindgren, Cecilia M., Welt, Corrine K., Diamanti-Kandarakis, Evanthia, Panidis, Dimitrios, Goodarzi, Mark O., Azziz, Ricardo, Zhang, Yi, James, Roland G., Olivier, Michael, Kissebah, Ahmed H., Stener-Victorin, Elisabet, Legro, Richard S., and Dunaif, Andrea

Published
2015
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48. Identification of cell surface markers to differentiate rat endothelial and fibroblast cells using lectin arrays and LC--ESI--MS/MS

Author

Lee, Ji Eun, Mirza, Shama P., Didier, Daniela N., Scalf, Mark, Olivier, Michael, Greene, Andrew S., and Smith, Lloyd M.

Subjects
Lectins -- Properties, Liquid chromatography -- Methods, Ionization -- Methods, Mass spectrometry -- Methods, Cell physiology -- Research, Epithelial cells -- Properties, Fibroblasts -- Properties, Chemistry
Abstract

Vascular endothelial cells located at the inner surface of blood vessels are a key component in angiogenesis and are employed as a primary cell type in the study of angiogenesis. These endothelial cells are, however, easily contaminated with fibroblast cells, which are located in proximity to the endothelial cells, during their isolation from tissue. It is thus important to find markers to distinguish the two cell types. In the present work, lectin arrays were prepared using aldehyde-terminated self-assembled monolayers (SAMs) and utilized to explore cell surface carbohydrate expression patterns on endothelial and fibroblast cells. It was found that the lectins Griffonia simplicifolia II (GS II) and Ulex europaeus agglutinin I (UEA I) selectively bind to rat fibroblast cells and not to rat endothelial cells. GS II-binding glycoproteins on fibroblast cells, which are potential cell surface markers to differentiate endothelial and fibroblast cells, were captured on a GS II lectin column and analyzed by LC-ESI-MS/MS. Six candidate cell surface glycoproteins were identified. Differential expression was confirmed by Western blot analysis for two of these proteins, lysosome-associated membrane glycoprotein-1 and transmembrane glycoprotein NMB.

Published
2008

49. Particle Size Distribution III

Author

Theodore Provder, M. Alexander, F. R. Hallett, D. G. Dalgleish, William B. Conklin, James P. Olivier, Michael L. Strickland, P. Sacoto, F. Lanza, H. Suarez, Luis H. Garcia-Rubio, C. Bacon, Luis H. Garcia-Rubio, Norman Ford, Trevor Havard, Peter Wallace, D. F. Nicoli, K. Hasapidis, P. O'Hagan, D. C.

Published
1998

50. Linkage and segregation analysis of black and brindle coat color in domestic dogs

Author

Kerns, Julie A., Cargill, Edward J., Clark, Leigh Anne, Candille, Sophie I., Berryere, Tom G., Olivier, Michael, Lust, George, Todhunter, Rory J., Schmutz, Sheila M., Murphy, Keith E., and Barsh, Gregory S.

Subjects
Dogs -- Genetic aspects, Allelomorphism -- Identification and classification, Pedigree analysis, Biological sciences
Abstract

Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red-yellow pheomelanin vs. black--brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching system is more complicated and fundamentally different from other mammals. Using a genomewide linkage scan on a Labrador X greyhound cross segregating for black, yellow, and brindle coat colors, we demonstrate that pigment type switching is controlled by an additional gene, the Klocus. Our results reveal three alleles with a dominance order of black ([K.sup.B]) > brindle ([k.sup.In] > yellow ([k.sup.v), whose genetic map position on dog chromosome 16 is distinct from the predicted location of other pigmentation genes. Interaction studies reveal that Mc1r is epistatic to variation at Agouti or Kand that the epistatic relationship between Agouti and Kdepends on the alleles being tested. These findings suggest a molecular model for a new component of the melanocortin signaling pathway and reveal how coat-color patterns and pigmentary diversity have been shaped by recent selection.

Published
2007

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