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6. A platform-independent AI tumor lineage and site (ATLAS) classifier

Author

Rydzewski, Nicholas R., Shi, Yue, Li, Chenxuan, Chrostek, Matthew R., Bakhtiar, Hamza, Helzer, Kyle T., Bootsma, Matthew L., Berg, Tracy J., Harari, Paul M., Floberg, John M., Blitzer, Grace C., Kosoff, David, Taylor, Amy K., Sharifi, Marina N., Yu, Menggang, Lang, Joshua M., Patel, Krishnan R., Citrin, Deborah E., Sundling, Kaitlin E., and Zhao, Shuang G.

Published
2024
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15. The All of Us Research Program: Data quality, utility, and diversity

Author

Ramirez, Andrea H, Sulieman, Lina, Schlueter, David J, Halvorson, Alese, Qian, Jun, Ratsimbazafy, Francis, Loperena, Roxana, Mayo, Kelsey, Basford, Melissa, Deflaux, Nicole, Muthuraman, Karthik N, Natarajan, Karthik, Kho, Abel, Xu, Hua, Wilkins, Consuelo, Anton-Culver, Hoda, Boerwinkle, Eric, Cicek, Mine, Clark, Cheryl R, Cohn, Elizabeth, Ohno-Machado, Lucila, Schully, Sheri D, Ahmedani, Brian K, Argos, Maria, Cronin, Robert M, O’Donnell, Christopher, Fouad, Mona, Goldstein, David B, Greenland, Philip, Hebbring, Scott J, Karlson, Elizabeth W, Khatri, Parinda, Korf, Bruce, Smoller, Jordan W, Sodeke, Stephen, Wilbanks, John, Hentges, Justin, Mockrin, Stephen, Lunt, Christopher, Devaney, Stephanie A, Gebo, Kelly, Denny, Joshua C, Carroll, Robert J, Glazer, David, Harris, Paul A, Hripcsak, George, Philippakis, Anthony, Roden, Dan M, Program, the All of Us Research, Ahmedani, Brian, Johnson, Christine D Cole, Ahsan, Habib, Antoine-LaVigne, Donna, Singleton, Glendora, Topol, Eric, Baca-Motes, Katie, Steinhubl, Steven, Wade, James, Begale, Mark, Jain, Praduman, Sutherland, Scott, Lewis, Beth, Behringer, Melissa, Gharavi, Ali G, Bier, Louise, Brilliant, Murray H, Murali, Narayana, Hebbring, Scott Joseph, Farrar-Edwards, Dorothy, Burnside, Elizabeth, Drezner, Marc K, Taylor, Amy, Channamsetty, Veena, Montalvo, Wanda, Sharma, Yashoda, Chinea, Carmen, Jenks, Nancy, Thibodeau, Steve, Holmes, Beverly Wilson, Schlueter, Eric, Collier, Ever, Winkler, Joyce, Corcoran, John, D’Addezio, Nick, Daviglus, Martha, Winn, Robert, Roden, Dan, Denny, Joshua, Doheny, Kim, Nickerson, Debbie, Eichler, Evan, Jarvik, Gail, and Funk, Gretchen

Subjects
Networking and Information Technology R&D (NITRD), Clinical Research, Cardiovascular, Cancer, Generic health relevance, Good Health and Well Being, All of Us Research Program, cloud-based analytics, cohort study, electronic health records, precision medicine
Abstract

The All of Us Research Program seeks to engage at least one million diverse participants to advance precision medicine and improve human health. We describe here the cloud-based Researcher Workbench that uses a data passport model to democratize access to analytical tools and participant information including survey, physical measurement, and electronic health record (EHR) data. We also present validation study findings for several common complex diseases to demonstrate use of this novel platform in 315,000 participants, 78% of whom are from groups historically underrepresented in biomedical research, including 49% self-reporting non-White races. Replication findings include medication usage pattern differences by race in depression and type 2 diabetes, validation of known cancer associations with smoking, and calculation of cardiovascular risk scores by reported race effects. The cloud-based Researcher Workbench represents an important advance in enabling secure access for a broad range of researchers to this large resource and analytical tools.

Published
2022

21. ASO Visual Abstract: Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma

Author

Marcinak, Clayton T., Praska, Corinne E., Vidri, Roberto J., Taylor, Amy K., Krebsbach, John K., Ahmed, Kaleem S., LoConte, Noelle K., Varley, Patrick R., Afshar, Majid, Weber, Sharon M., Abbott, Daniel E., Mathew, Jomol, Murtaza, Muhammed, Burkard, Mark E., Churpek, Matthew M., and Zafar, Syed Nabeel

Published
2024
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24. Phases of the Moon: As Simple as ABCDE Teaching the Phases of the Moon to First Graders Using Patterns

Author

Blum, Caleigh and Taylor, Amy

Abstract

Children are very curious about the world around them. You may find them peering at tadpoles in a pond, counting ants on a log, or wondering about the stars, the sun, and the moon. I have been asked many times: Is the moon really made of cheese? Do astronauts live on the moon? Why does the moon look different every time I look up? Introducing young learners to our universe, beyond what their eyes can see, is a powerful teaching moment that primary teachers like myself get the pleasure to experience. Fostering students' early curiosities regarding our universe is one of the first steps to opening their minds to the vision of endless possibilities. Making observations, asking questions, and recognizing patterns are a few of the initial skills a young science learner should be encouraged to practice. In this particular unit, first grade students make observations of the sky including the differences in features and apparent movement of celestial objects. This unit and the featured lesson emphasize the use of students' prior knowledge and observations of the sky and identifying patterns to predict and infer how the moon changes during the lunar cycle.

Published
2022
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25. Genetic diversity fuels gene discovery for tobacco and alcohol use

Author

Saunders, Gretchen R. B., Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M., Addison, Clifton, Akiyama, Masato, Albert, Christine M., Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K., Ashley-Koch, Allison E., Ashrani, Aneel A., Barnes, Kathleen C., Barr, R. Graham, Bartz, Traci M., Becker, Diane M., Bielak, Lawrence F., Benjamin, Emelia J., Bis, Joshua C., Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R., Boardman, Jason D., Boerwinkle, Eric, Boomsma, Dorret I., Boorgula, Meher Preethi, Bowden, Donald W., Brody, Jennifer A., Cade, Brian E., Chasman, Daniel I., Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H., Choquet, Hélène, Cole, John W., Cornelis, Marilyn C., Cucca, Francesco, Curran, Joanne E., de Andrade, Mariza, Dick, Danielle M., Docherty, Anna R., Duggirala, Ravindranath, Eaton, Charles B., Ehringer, Marissa A., Esko, Tõnu, Faul, Jessica D., Silva, Lilian Fernandes, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I., Gabrielsen, Maiken E., Garrett, Melanie E., Gharib, Sina A., Gieger, Christian, Gillespie, Nathan, Glahn, David C., Gordon, Scott D., Gu, Charles C., Gu, Dongfeng, Gudbjartsson, Daniel F., Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E., Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K., Hickie, Ian, Hidalgo, Bertha, Hokanson, John E., Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J., Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R., Jee, Yon Ho, Johnson, Eric O., Joo, Yoonjung Y., Jorgenson, Eric, Justice, Anne E., Kamatani, Yoichiro, Kaplan, Robert C., Kaprio, Jaakko, Kardia, Sharon L. R., Keller, Matthew C., Kelly, Tanika N., Kooperberg, Charles, Korhonen, Tellervo, Kraft, Peter, Krauter, Kenneth, Kuusisto, Johanna, Laakso, Markku, Lasky-Su, Jessica, Lee, Wen-Jane, Lee, James J., Levy, Daniel, Li, Liming, Li, Kevin, Li, Yuqing, Lin, Kuang, Lind, Penelope A., Liu, Chunyu, Lloyd-Jones, Donald M., Lutz, Sharon M., Ma, Jiantao, Mägi, Reedik, Manichaikul, Ani, Martin, Nicholas G., Mathur, Ravi, Matoba, Nana, McArdle, Patrick F., McGue, Matt, McQueen, Matthew B., Medland, Sarah E., Metspalu, Andres, Meyers, Deborah A., Millwood, Iona Y., Mitchell, Braxton D., Mohlke, Karen L., Moll, Matthew, Montasser, May E., Morrison, Alanna C., Mulas, Antonella, Nielsen, Jonas B., North, Kari E., Oelsner, Elizabeth C., Okada, Yukinori, Orrù, Valeria, Palmer, Nicholette D., Palviainen, Teemu, Pandit, Anita, Park, S. Lani, Peters, Ulrike, Peters, Annette, Peyser, Patricia A., Polderman, Tinca J. C., Rafaels, Nicholas, Redline, Susan, Reed, Robert M., Reiner, Alex P., Rice, John P., Rich, Stephen S., Richmond, Nicole E., Roan, Carol, Rotter, Jerome I., Rueschman, Michael N., Runarsdottir, Valgerdur, Saccone, Nancy L., Schwartz, David A., Shadyab, Aladdin H., Shi, Jingchunzi, Shringarpure, Suyash S., Sicinski, Kamil, Skogholt, Anne Heidi, Smith, Jennifer A., Smith, Nicholas L., Sotoodehnia, Nona, Stallings, Michael C., Stefansson, Hreinn, Stefansson, Kari, Stitzel, Jerry A., Sun, Xiao, Syed, Moin, Tal-Singer, Ruth, Taylor, Amy E., Taylor, Kent D., Telen, Marilyn J., Thai, Khanh K., Tiwari, Hemant, Turman, Constance, Tyrfingsson, Thorarinn, Wall, Tamara L., Walters, Robin G., Weir, David R., Weiss, Scott T., White, Wendy B., Whitfield, John B., Wiggins, Kerri L., Willemsen, Gonneke, Willer, Cristen J., Winsvold, Bendik S., Xu, Huichun, Yanek, Lisa R., Yin, Jie, Young, Kristin L., Young, Kendra A., Yu, Bing, Zhao, Wei, Zhou, Wei, Zöllner, Sebastian, Zuccolo, Luisa, Batini, Chiara, Bergen, Andrew W., Bierut, Laura J., David, Sean P., Gagliano Taliun, Sarah A., Hancock, Dana B., Jiang, Bibo, Munafò, Marcus R., Thorgeirsson, Thorgeir E., Liu, Dajiang J., and Vrieze, Scott

Published
2022
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28. Reduced C9ORF72 function exacerbates gain of toxicity from ALS/FTD-causing repeat expansion in C9orf72

Author

Zhu, Qiang, Jiang, Jie, Gendron, Tania F, McAlonis-Downes, Melissa, Jiang, Lulin, Taylor, Amy, Diaz Garcia, Sandra, Ghosh Dastidar, Somasish, Rodriguez, Maria J, King, Patrick, Zhang, Yongjie, La Spada, Albert R, Xu, Huaxi, Petrucelli, Leonard, Ravits, John, Da Cruz, Sandrine, Lagier-Tourenne, Clotilde, and Cleveland, Don W

Subjects
Genetics, Neurosciences, Neurodegenerative, Aging, Orphan Drug, Dementia, Rare Diseases, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Alzheimer's Disease Related Dementias (ADRD), Frontotemporal Dementia (FTD), ALS, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Neurological, Amyotrophic Lateral Sclerosis, Animals, C9orf72 Protein, DNA Repeat Expansion, Female, Frontotemporal Dementia, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Hexanucleotide expansions in C9orf72, which encodes a predicted guanine exchange factor, are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although repeat expansion has been established to generate toxic products, mRNAs encoding the C9ORF72 protein are also reduced in affected individuals. In this study, we tested how C9ORF72 protein levels affected repeat-mediated toxicity. In somatic transgenic mice expressing 66 GGGGCC repeats, inactivation of one or both endogenous C9orf72 alleles provoked or accelerated, respectively, early death. In mice expressing a C9orf72 transgene with 450 repeats that did not encode the C9ORF72 protein, inactivation of one or both endogenous C9orf72 alleles exacerbated cognitive deficits, hippocampal neuron loss, glial activation and accumulation of dipeptide-repeat proteins from translation of repeat-containing RNAs. Reduced C9ORF72 was shown to suppress repeat-mediated elevation in autophagy. These efforts support a disease mechanism in ALS/FTD resulting from reduced C9ORF72, which can lead to autophagy deficits, synergizing with repeat-dependent gain of toxicity.

Published
2020

29. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Author

Liu, Mengzhen, Jiang, Yu, Wedow, Robbee, Li, Yue, Brazel, David M, Chen, Fang, Datta, Gargi, Davila-Velderrain, Jose, McGuire, Daniel, Tian, Chao, Zhan, Xiaowei, Choquet, Hélène, Docherty, Anna R, Faul, Jessica D, Foerster, Johanna R, Fritsche, Lars G, Gabrielsen, Maiken Elvestad, Gordon, Scott D, Haessler, Jeffrey, Hottenga, Jouke-Jan, Huang, Hongyan, Jang, Seon-Kyeong, Jansen, Philip R, Ling, Yueh, Mägi, Reedik, Matoba, Nana, McMahon, George, Mulas, Antonella, Orrù, Valeria, Palviainen, Teemu, Pandit, Anita, Reginsson, Gunnar W, Skogholt, Anne Heidi, Smith, Jennifer A, Taylor, Amy E, Turman, Constance, Willemsen, Gonneke, Young, Hannah, Young, Kendra A, Zajac, Gregory JM, Zhao, Wei, Zhou, Wei, Bjornsdottir, Gyda, Boardman, Jason D, Boehnke, Michael, Boomsma, Dorret I, Chen, Chu, Cucca, Francesco, Davies, Gareth E, Eaton, Charles B, Ehringer, Marissa A, Esko, Tõnu, Fiorillo, Edoardo, Gillespie, Nathan A, Gudbjartsson, Daniel F, Haller, Toomas, Harris, Kathleen Mullan, Heath, Andrew C, Hewitt, John K, Hickie, Ian B, Hokanson, John E, Hopfer, Christian J, Hunter, David J, Iacono, William G, Johnson, Eric O, Kamatani, Yoichiro, Kardia, Sharon LR, Keller, Matthew C, Kellis, Manolis, Kooperberg, Charles, Kraft, Peter, Krauter, Kenneth S, Laakso, Markku, Lind, Penelope A, Loukola, Anu, Lutz, Sharon M, Madden, Pamela AF, Martin, Nicholas G, McGue, Matt, McQueen, Matthew B, Medland, Sarah E, Metspalu, Andres, Mohlke, Karen L, Nielsen, Jonas B, Okada, Yukinori, Peters, Ulrike, Polderman, Tinca JC, Posthuma, Danielle, Reiner, Alexander P, Rice, John P, Rimm, Eric, Rose, Richard J, Runarsdottir, Valgerdur, Stallings, Michael C, Stančáková, Alena, Stefansson, Hreinn, Thai, Khanh K, Tindle, Hilary A, Tyrfingsson, Thorarinn, and Wall, Tamara L

Subjects
Substance Misuse, Human Genome, Brain Disorders, Tobacco, Tobacco Smoke and Health, Genetics, Alcoholism, Alcohol Use and Health, Prevention, Aetiology, 2.1 Biological and endogenous factors, Stroke, Cancer, Cardiovascular, Good Health and Well Being, Alcohol Drinking, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Phenotype, Risk, Smoking, Tobacco Use Disorder, 23andMe Research Team, HUNT All-In Psychiatry, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.

Published
2019

30. The All of Us Research Program: Data quality, utility, and diversity

Author

Ahmedani, Brian, Cole Johnson, Christine D., Ahsan, Habib, Antoine-LaVigne, Donna, Singleton, Glendora, Anton-Culver, Hoda, Topol, Eric, Baca-Motes, Katie, Steinhubl, Steven, Wade, James, Begale, Mark, Jain, Praduman, Sutherland, Scott, Lewis, Beth, Korf, Bruce, Behringer, Melissa, Gharavi, Ali G., Goldstein, David B., Hripcsak, George, Bier, Louise, Boerwinkle, Eric, Brilliant, Murray H., Murali, Narayana, Hebbring, Scott Joseph, Farrar-Edwards, Dorothy, Burnside, Elizabeth, Drezner, Marc K., Taylor, Amy, Channamsetty, Veena, Montalvo, Wanda, Sharma, Yashoda, Chinea, Carmen, Jenks, Nancy, Cicek, Mine, Thibodeau, Steve, Holmes, Beverly Wilson, Schlueter, Eric, Collier, Ever, Winkler, Joyce, Corcoran, John, D’Addezio, Nick, Daviglus, Martha, Winn, Robert, Wilkins, Consuelo, Roden, Dan, Denny, Joshua, Doheny, Kim, Nickerson, Debbie, Eichler, Evan, Jarvik, Gail, Funk, Gretchen, Philippakis, Anthony, Rehm, Heidi, Lennon, Niall, Kathiresan, Sekar, Gabriel, Stacey, Gibbs, Richard, Gil Rico, Edgar M., Glazer, David, Grand, Joannie, Greenland, Philip, Harris, Paul, Shenkman, Elizabeth, Hogan, William R., Igho-Pemu, Priscilla, Pollan, Cliff, Jorge, Milena, Okun, Sally, Karlson, Elizabeth W., Smoller, Jordan, Murphy, Shawn N., Ross, Margaret Elizabeth, Kaushal, Rainu, Winford, Eboni, Wallace, Febe, Khatri, Parinda, Kheterpal, Vik, Ojo, Akinlolu, Moreno, Francisco A., Kron, Irving, Peterson, Rachele, Menon, Usha, Lattimore, Patricia Watkins, Leviner, Noga, Obedin-Maliver, Juno, Lunn, Mitchell, Malik-Gagnon, Lynda, Mangravite, Lara, Marallo, Adria, Marroquin, Oscar, Visweswaran, Shyam, Reis, Steven, Marshall, Gailen, Jr., McGovern, Patrick, Mignucci, Deb, Moore, John, Munoz, Fatima, Talavera, Gregory, O'Connor, George T., O'Donnell, Christopher, Ohno-Machado, Lucila, Orr, Greg, Randal, Fornessa, Theodorou, Andreas A., Reiman, Eric, Roxas-Murray, Mercedita, Stark, Louisa, Tepp, Ronnie, Zhou, Alicia, Topper, Scott, Trousdale, Rhonda, Tsao, Phil, Weidman, Lisa, Weiss, Scott T., Wellis, David, Whittle, Jeffrey, Wilson, Amanda, Zuchner, Stephan, Zwick, Michael E., Ramirez, Andrea H., Sulieman, Lina, Schlueter, David J., Halvorson, Alese, Qian, Jun, Ratsimbazafy, Francis, Loperena, Roxana, Mayo, Kelsey, Basford, Melissa, Deflaux, Nicole, Muthuraman, Karthik N., Natarajan, Karthik, Kho, Abel, Xu, Hua, Clark, Cheryl R., Cohn, Elizabeth, Schully, Sheri D., Ahmedani, Brian K., Argos, Maria, Cronin, Robert M., O’Donnell, Christopher, Fouad, Mona, Hebbring, Scott J., Smoller, Jordan W., Sodeke, Stephen, Wilbanks, John, Hentges, Justin, Mockrin, Stephen, Lunt, Christopher, Devaney, Stephanie A., Gebo, Kelly, Denny, Joshua C., Carroll, Robert J., Harris, Paul A., and Roden, Dan M.

Published
2022
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32. BRCA-DIRECT digital pathway for diagnostic germline genetic testing within a UK breast oncology setting: a randomised, non-inferiority trial.

Author

Torr, Bethany, Jones, Christopher, Kavanaugh, Grace, Hamill, Monica, Allen, Sophie, Choi, Subin, Garrett, Alice, Valganon-Petrizan, Mikel, MacMahon, Suzanne, Yuan, Lina, Way, Rosalind, Harder, Helena, Gold, Rochelle, Taylor, Amy, Gabe, Rhian, Lucassen, Anneke, Manchanda, Ranjit, Fallowfield, Lesley, Jenkins, Valerie, and Gandhi, Ashu

Abstract

Background: Genetic testing to identify germline high-risk pathogenic variants in breast cancer susceptibility genes is increasingly part of the breast cancer diagnostic pathway. Novel patient-centred pathways may offer opportunity to expand capacity and reduce turnaround time. Methods: We recruited 1140 women with unselected breast cancer to undergo germline genetic testing through the BRCA-DIRECT pathway (which includes a digital platform, postal saliva sampling and a genetic counsellor telephone helpline). Ahead of consenting to the test, participants were randomised to receive information about genetic testing digitally (569/1140, 49.9%) or via a pre-test genetic counselling consultation (571/1140, 50.1%). Results: 1001 (87.8%) participants progressed to receive their pre-test information and consented to testing. The primary outcome, uptake of genetic testing, was higher amongst participants randomised to receive digital information compared with those randomised to a pre-test genetic counselling consultation (90.8% (95% CI: 88.5% to 93.1%) vs 84.7% (95% CI: 81.8% to 87.6%), p = 0.002, adjusted for participant age and site). Non-inferiority was observed in relation to patient knowledge, anxiety, and satisfaction. Conclusions: Findings demonstrate that standardised, digital information offers a non-inferior alternative to conventional genetic counselling, and an end-to-end patient-centred, digital pathway (supported by genetic counselling hotline) could feasibly be implemented into breast oncology settings. Clinical trial registration: The study is registered with, and protocol available on, ClinicalTrials.gov (NCT04842799). [ABSTRACT FROM AUTHOR]

Published
2024
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33. 'I Could See Myself as a Scientist': The Potential of Out-of-School Time Programs to Influence Girls' Identities in Science

Author

Riedinger, Kelly and Taylor, Amy

Abstract

Out-of-school time (OST) programs like the Coastal Ecology science camp can positively influence science identities, particularly for youth from groups historically underserved and underrepresented in science, technology, engineering, and math (STEM). OST STEM programming gives youth opportunities to learn science outside the formal classroom in such settings as afterschool programs, science camps, outreach programs, internships, and scouting. OST science programs often do not formally assess participants or assign grades. They provide opportunities for authentic, meaningful learning that may be more comfortable for some youth than school curricula. Further, OST programs may give youth access to resources and to scientific practices and tools not typically available in classrooms. This access may be especially important for youth from underresourced schools. Many programs allow youth to explore science in ways that support their identities. The study presented in this article explored how the Coastal Ecology science camp helped participants, specifically girls, develop science identities. It also studied how the girls' social interactions supported their identities as learners of science.

Published
2016

34. Lost and found: The slave trader's hymn that inspired the enslaved

Author

Taylor, Amy Murrell

Subjects
University of California Press, Publishing industry, Publishing industry, Literature/writing
Abstract

AMAZING GRACE A cultural history of the beloved hymn JAMES WALVIN 216pp. University of California Press. 16.99 [pounds sterling] (US $19.95). 'Amazing Grace' has had an unusually long life. First [...]

Published
2024

35. Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 amyotrophic lateral sclerosis

Author

Saberi, Shahram, Stauffer, Jennifer E, Jiang, Jie, Garcia, Sandra Diaz, Taylor, Amy E, Schulte, Derek, Ohkubo, Takuya, Schloffman, Cheyenne L, Maldonado, Marcus, Baughn, Michael, Rodriguez, Maria J, Pizzo, Don, Cleveland, Don, and Ravits, John

Subjects
Acquired Cognitive Impairment, Brain Disorders, Neurosciences, Dementia, Rare Diseases, ALS, Neurodegenerative, Neurological, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Brain, C9orf72 Protein, Cell Nucleus, Cytoplasm, DNA Repeat Expansion, DNA-Binding Proteins, Dendrites, Dipeptides, Female, Humans, Male, Middle Aged, Nerve Degeneration, Neuroglia, Spinal Cord, C9orf72, Hexanucleotide repeat expansions, Amyotrophic lateral sclerosis, Dipeptide repeat proteins, Arginine-containing dipeptide repeat proteins, Poly-GR, Sense strand, Antisense strand, Nuclear pore complex and nucleocytoplasmic transport, Clinical Sciences, Neurology & Neurosurgery
Abstract

Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically related and clinically unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically related areas compared to unrelated areas (p

Published
2018

36. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

Author

Adams, Lisa, Adlard, Julian, Alfonso, Rosa, Ali, Saira, Andrew, Angela, Araújo, Luís, Azam, Nazya, Ball, Darran, Barker, Queenstone, Basevitch, Alon, Benton, Barbara, Berlin, Cheryl, Bermingham, Nicola, Biller, Leah, Bloss, Angela, Bradford, Matilda, Bradshaw, Nicola, Branson, Amy, Brendler, Charles, Brennan, Maria, Bulman, Barbara, Burgess, Lucy, Cahill, Declan, Callard, Alice, Calvo Verges, Nuria, Cardoso, Marta, Carter, Vanda, Catanzaro, Mario, Chamberlain, Anthony, Chapman, Cyril, Chong, Michael, Clark, Caroline, Clowes, Virginia, Cogley, Lyn, Cole, Trevor, Compton, Cecilia, Conner, Tom, Cookson, Sandra, Cornford, Philip, Costello, Philandra, Coulier, Laura, Davies, Michaela, Dechet, Christopher, DeSouza, Bianca, Devlin, Gemma, Douglas, Fiona, Douglas, Emma, Dudakia, Darshna, Duncan, Alexis, Ellery, Natalie, Everest, Sarah, Freemantle, Sue, Frydenberg, Mark, Fuller, Debbie, Gabriel, Camila, Gale, Madeline, Garcia, Lynda, Gay, Simona, Genova, Elena, George, Angela, Georgiou, Demetra, Gisbert, Alexandra, Gleeson, Margaret, Glover, Wayne, Gnanapragasam, Vincent, Goff, Sally, Goldgar, David, Gonçalves, Nuno, Goodman, Selina, Gorrie, Jennifer, Gott, Hannah, Grant, Anna, Gray, Catherine, Griffiths, Julie, Gupwell, Karin, Gurasashvili, Jana, Hanslien, Eldbjørg, Haraldsdottir, Sigurdis, Hart, Rachel, Hartigan, Catherine, Hawkes, Lara, Heaton, Tricia, Henderson, Alex, Henrique, Rui, Hilario, Kathrine, Hill, Kathryn, Hulick, Peter, Hunt, Clare, Hutchings, Melanie, Ibitoye, Rita, Inglehearn, Thomas, Ireland, Joanna, Islam, Farah, Ismail, Siti, Jacobs, Chris, James, Denzil, Jenkins, Sharon, Jobson, Irene, Johnstone, Anne, Jones, Oliver, Josefsberg Ben-Yehoshua, Sagi, Kaemba, Beckie, Kaul, Karen, Kemp, Zoe, Kinsella, Netty, Klehm, Margaret, Kockelbergh, Roger, Kohut, Kelly, Kosicka-Slawinska, Monika, Kulkarni, Anjana, Kumar, Pardeep, Lam, Jimmy, LeButt, Mandy, Leibovici, Dan, Lim, Ramona, Limb, Lauren, Lomas, Claire, Longmuir, Mark, López, Consol, Magnani, Tiziana, Maia, Sofia, Maiden, Jessica, Male, Alison, Manalo, Merrie, Martin, Phoebe, McBride, Donna, McGuire, Michael, McMahon, Romayne, McNally, Claire, McVeigh, Terri, Melzer, Ehud, Mencias, Mark, Mercer, Catherine, Mitchell, Gillian, Mora, Josefina, Morton, Catherine, Moss, Cathryn, Murphy, Morgan, Murphy, Declan, Mzazi, Shumi, Nadolski, Maria, Newlin, Anna, Nogueira, Pedro, O'Keefe, Rachael, O'Toole, Karen, O'Connell, Shona, Ogden, Chris, Okoth, Linda, Oliveira, Jorge, Paez, Edgar, Palou, Joan, Park, Linda, Patel, Nafisa, Paulo Souto, João, Pearce, Allison, Peixoto, Ana, Perez, Kimberley, Petelin, Lara, Pichert, Gabriella, Poile, Charlotte, Potter, Alison, Preitner, Nadia, Purnell, Helen, Quinn, Ellen, Radice, Paolo, Rankin, Brigette, Rees, Katie, Renton, Caroline, Richardson, Kate, Risby, Peter, Rogers, Jason, Ruderman, Maggie, Ruiz, April, Sajoo, Anaar, Salvatore, Natale, Sands, Victoria, Sanguedolce, Francesco, Sattar, Ayisha, Saunders, Kathryn, Schofield, Lyn, Scott, Rodney, Searle, Anne, Sehra, Ravinder, Selkirk, Christina, Shackleton, Kylie, Shanley, Sue, Shaw, Adam, Shevrin, Daniel, Shipman, Hannah, Sidat, Zahirah, Siguake, Kas, Simon, Kate, Smyth, Courtney, Snadden, Lesley, Solanky, Nita, Solomons, Joyce, Sorrentino, Margherita, Stayner, Barbara, Stephenson, Robert, Stoffel, Elena, Thomas, Maggie, Thompson, Alan, Tidey, Lizzie, Tischkowitz, Marc, Torokwa, Audrey, Townshend, Sharron, Treherne, Katy, Tricker, Karen, Trinh, Quoc-Dien, Tripathi, Vishakha, Turnbull, Clare, Valdagni, Riccardo, Van As, Nicholas, Venne, Vickie, Verdon, Lizzie, Vitellaro, Marco, Vogel, Kristen, Walker, Lisa, Watford, Amy, Watt, Cathy, Weintroub, Ilana, Weiss, Shelly, Weissman, Scott, Weston, Michelle, Wiggins, Jennifer, Wise, Gillian, Woodhouse, Christopher, Yesildag, Pembe, Youngs, Alice, Yurgelun, Matthew, Zollo, Fabiana, Bancroft, Elizabeth K, Page, Elizabeth C, Brook, Mark N, Thomas, Sarah, Taylor, Natalie, Pope, Jennifer, McHugh, Jana, Jones, Ann-Britt, Karlsson, Questa, Merson, Susan, Ong, Kai Ren, Hoffman, Jonathan, Huber, Camilla, Maehle, Lovise, Grindedal, Eli Marie, Stormorken, Astrid, Evans, D Gareth, Rothwell, Jeanette, Lalloo, Fiona, Brady, Angela F, Bartlett, Marion, Snape, Katie, Hanson, Helen, James, Paul, McKinley, Joanne, Mascarenhas, Lyon, Syngal, Sapna, Ukaegbu, Chinedu, Side, Lucy, Thomas, Tessy, Barwell, Julian, Teixeira, Manuel R, Izatt, Louise, Suri, Mohnish, Macrae, Finlay A, Poplawski, Nicola, Chen-Shtoyerman, Rakefet, Ahmed, Munaza, Musgrave, Hannah, Nicolai, Nicola, Greenhalgh, Lynn, Brewer, Carole, Pachter, Nicholas, Spigelman, Allan D, Azzabi, Ashraf, Helfand, Brian T, Halliday, Dorothy, Buys, Saundra, Ramon y Cajal, Teresa, Donaldson, Alan, Cooney, Kathleen A, Harris, Marion, McGrath, John, Davidson, Rosemarie, Taylor, Amy, Cooke, Peter, Myhill, Kathryn, Hogben, Matthew, Aaronson, Neil K, Ardern-Jones, Audrey, Bangma, Chris H, Castro, Elena, Dearnaley, David, Dias, Alexander, Dudderidge, Tim, Eccles, Diana M, Green, Kate, Eyfjord, Jorunn, Falconer, Alison, Foster, Christopher S, Gronberg, Henrik, Hamdy, Freddie C, Johannsson, Oskar, Khoo, Vincent, Lilja, Hans, Lindeman, Geoffrey J, Lubinski, Jan, Axcrona, Karol, Mikropoulos, Christos, Mitra, Anita V, Moynihan, Clare, Ni Raghallaigh, Holly, Rennert, Gad, Collier, Rebecca, Offman, Judith, Kote-Jarai, Zsofia, and Eeles, Rosalind A

Published
2021
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38. Sponsored Projects : The NOAA Office of Ocean Exploration and Research

Author

Valette-Silver, Nathalie, Hammond, Stephen R., Cantelas, Frank, Beaverson, Chris, Copeland, Adrienne, Egan, Katharine, Netburn, Amanda N., Bohan, Margot, Jefferson, Yvette, Woodford, Joyce, Voss, Joshua, Pomponi, Shirley, Iken, Katrin, Smith, John R., Watling, Les, Summers, Natalie, Roark, E. Brendan, Morgan, Nicole, Lensing, Becca, France, Scott C., Dulai, Henrietta, Carter, Glenn S., Bingo, Sarah, Baco-Taylor, Amy, German, Christopher R., Johnsen, Sönke, Hall, Emily R., Culter, Jim, Beckler, Jordon, Talliefert, Martial, Stewart, Frank, Smith, Chris, Hamdan, Leila, Evans, Amanda, Kaiser, Carl L., Lindzey, Laura, Jakuba, Michael V., Partan, James W., and Dolan, Christopher

Published
2020

39. Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia

Author

Pappalardi, Melissa B., Keenan, Kathryn, Cockerill, Mark, Kellner, Wendy A., Stowell, Alexandra, Sherk, Christian, Wong, Kristen, Pathuri, Sarath, Briand, Jacques, Steidel, Michael, Chapman, Philip, Groy, Arthur, Wiseman, Ashley K., McHugh, Charles F., Campobasso, Nino, Graves, Alan P., Fairweather, Emma, Werner, Thilo, Raoof, Ali, Butlin, Roger J., Rueda, Lourdes, Horton, John R., Fosbenner, David T., Zhang, Cunyu, Handler, Jessica L., Muliaditan, Morris, Mebrahtu, Makda, Jaworski, Jon-Paul, McNulty, Dean E., Burt, Charlotte, Eberl, H. Christian, Taylor, Amy N., Ho, Thau, Merrihew, Susan, Foley, Shawn W., Rutkowska, Anna, Li, Mei, Romeril, Stuart P., Goldberg, Kristin, Zhang, Xing, Kershaw, Christopher S., Bantscheff, Marcus, Jurewicz, Anthony J., Minthorn, Elisabeth, Grandi, Paola, Patel, Mehul, Benowitz, Andrew B., Mohammad, Helai P., Gilmartin, Aidan G., Prinjha, Rab K., Ogilvie, Donald, Carpenter, Christopher, Heerding, Dirk, Baylin, Stephen B., Jones, Peter A., Cheng, Xiaodong, King, Bryan W., Luengo, Juan I., Jordan, Allan M., Waddell, Ian, Kruger, Ryan G., and McCabe, Michael T.

Published
2021
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42. Management of intussusception in children: A systematic review

Author

Kelley-Quon, Lorraine I., Arthur, L. Grier, Williams, Regan F., Goldin, Adam B., St. Peter, Shawn D., Beres, Alana L., Hu, Yue-Yung, Renaud, Elizabeth J., Ricca, Robert, Slidell, Mark B., Taylor, Amy, Smith, Caitlin A., Miniati, Doug, Sola, Juan E., Valusek, Patricia, Berman, Loren, Raval, Mehul V., Gosain, Ankush, Dellinger, Matthew B., Sømme, Stig, Downard, Cynthia D., McAteer, Jarod P., and Kawaguchi, Akemi

Published
2021
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47. Epigenetic Regulation of F2RL3 Associates with Myocardial Infarction and Platelet Function

Author

Corbin, Laura J., White, Stephen J., Taylor, Amy E., Williams, Christopher M., Taylor, Kurt, van den Bosch, Marion T., Teasdale, Jack E., Jones, Matthew, Bond, Mark, Harper, Matthew T., Falk, Louise, Groom, Alix, Hazell, Georgina G J, Paternoster, Lavinia, Munafò, Marcus R., Nordestgaard, Børge G., Tybjærg-Hansen, Anne, Bojesen, Stig E., Relton, Caroline, Min, Josine L., Smith, George Davey, Mumford, Andrew D., Poole, Alastair W., and Timpson, Nicholas J.

Published
2022
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48. Sphingosine 1-phosphate elicits RhoA-dependent proliferation and MRTF-A mediated gene induction in CPCs

Author

Castaldi, Alessandra, Chesini, Gino P, Taylor, Amy E, Sussman, Mark A, Brown, Joan Heller, and Purcell, Nicole H

Subjects
Stem Cell Research, Cardiovascular, Heart Disease, Underpinning research, 1.1 Normal biological development and functioning, Animals, Biomarkers, Cell Lineage, Cell Nucleus, Cell Proliferation, Lysophospholipids, Male, Mice, Knockout, Myocardium, RNA, Messenger, Receptors, G-Protein-Coupled, Receptors, Lysosphingolipid, Serum Response Factor, Sphingosine, Stem Cells, Trans-Activators, Transcription, Genetic, Transcriptional Activation, rhoA GTP-Binding Protein, Sphingosine-1-phosphate, GPCR, Cardiac progenitor cells, MRTF-A, RhoA, Biochemistry and Cell Biology, Medical Physiology, Biochemistry & Molecular Biology
Abstract

Although c-kit(+) cardiac progenitor cells (CPCs) are currently used in clinical trials there remain considerable gaps in our understanding of the molecular mechanisms underlying their proliferation and differentiation. G-protein coupled receptors (GPCRs) play an important role in regulating these processes in mammalian cell types thus we assessed GPCR mRNA expression in c-kit(+) cells isolated from adult mouse hearts. Our data provide the first comprehensive overview of the distribution of this fundamental class of cardiac receptors in CPCs and reveal notable distinctions from that of adult cardiomyocytes. We focused on GPCRs that couple to RhoA activation in particular those for sphingosine-1-phosphate (S1P). The S1P2 and S1P3 receptors are the most abundant S1P receptor subtypes in mouse and human CPCs while cardiomyocytes express predominantly S1P1 receptors. Treatment of CPCs with S1P, as with thrombin and serum, increased proliferation through a pathway requiring RhoA signaling, as evidenced by significant attenuation when Rho was inhibited by treatment with C3 toxin. Further analysis demonstrated that both S1P- and serum-induced proliferation are regulated through the S1P2 and S1P3 receptor subtypes which couple to Gα12/13 to elicit RhoA activation. The transcriptional co-activator MRTF-A was activated by S1P as assessed by its nuclear accumulation and induction of a RhoA/MRTF-A luciferase reporter. In addition S1P treatment increased expression of cardiac lineage markers Mef2C and GATA4 and the smooth muscle marker GATA6 through activation of MRTF-A. In conclusion, we delineate an S1P-regulated signaling pathway in CPCs that introduces the possibility of targeting S1P2/3 receptors, Gα12/13 or RhoA to influence the proliferation and commitment of c-kit(+) CPCs and improve the response of the myocardium following injury.

Published
2016

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