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3. Design and Synthesis of Clinical Candidate PF-06852231 (CVL-231): A Brain Penetrant, Selective, Positive Allosteric Modulator of the M4 Muscarinic Acetylcholine Receptor.

Author

Butler, Christopher R., Popiolek, Michael, McAllister, Laura A., LaChapelle, Erik A., Kramer, Melissa, Beck, Elizabeth M., Mente, Scot, Brodney, Michael A., Brown, Matthew, Gilbert, Adam, Helal, Chris, Ogilvie, Kevin, Starr, Jeremy, Uccello, Daniel, Grimwood, Sarah, Edgerton, Jeremy, Garst-Orozco, Jonathan, Kozak, Rouba, Lotarski, Susan, and Rossi, Amie

Published
2024
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4. Evaluating the quality of life impact of recurrent urinary tract infection: Validation and refinement of the Recurrent UTI Impact Questionnaire (RUTIIQ).

Author

Newlands, Abigail F., Kramer, Melissa, Roberts, Lindsey, Maxwell, Kayleigh, Price, Jessica L., and Finlay, Katherine A.

Subjects
URINARY tract infections, QUALITY of life, PATIENT experience, PATIENT reported outcome measures, PSYCHOMETRICS
Abstract

Background and Aims: Recurrent urinary tract infection (rUTI) has significant negative consequences for a wide variety of quality of life (QoL) domains. Without adequate validation and assessment of the unique insights of people living with rUTI, clinical results cannot be fully understood. The Recurrent UTI Impact Questionnaire (RUTIIQ), a novel patient‐reported outcome measure of rUTI psychosocial impact, has been robustly developed with extensive patient and clinician input to facilitate enhanced rUTI management and research. This study aimed to confirm the structural validity of the RUTIIQ, assessing its strength and bifactor model fit. Methods: A sample of 389 adults experiencing rUTI (96.9% female, aged 18–87 years) completed an online cross‐sectional survey comprising a demographic questionnaire and the RUTIIQ. A bifactor graded response model was fitted to the data, optimizing the questionnaire structure based on item fit, discrimination capability, local dependence, and differential item functioning. Results: The final RUTIIQ demonstrated excellent bifactor model fit (RMSEA = 0.054, CFI = 0.99, SRMSR = 0.052), and mean‐square fit indices indicated that all included items were productive for measurement (MNSQ = 0.52–1.41). The final questionnaire comprised an 18‐item general "rUTI QoL impact" factor, and five subfactor domains measuring "personal wellbeing" (three items), "social wellbeing" (four items), "work and activity interference" (four items), "patient satisfaction" (four items), and "sexual wellbeing" (three items). Together, the general factor and five subfactors explained 81.6% of the common model variance. All factor loadings were greater than 0.30 and communalities greater than 0.60, indicating good model fit and structural validity. Conclusions: The 18‐item RUTIIQ is a robust, patient‐tested questionnaire with excellent psychometric properties, which capably assesses the patient experience of rUTI‐related impact to QoL and healthcare satisfaction. Facilitating standardized patient monitoring and improved shared decision‐making, the RUTIIQ delivers the unique opportunity to improve patient‐centered care. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer

Author

Tamura, Koji, Yu, Jun, Hata, Tatsuo, Suenaga, Masaya, Shindo, Koji, Abe, Toshiya, MacGregor-Das, Anne, Borges, Michael, Wolfgang, Christopher L., Weiss, Matthew J., He, Jin, Canto, Marcia Irene, Petersen, Gloria M., Gallinger, Steven, Syngal, Sapna, Brand, Randall E., Rustgi, Anil, Olson, Sara H., Stoffel, Elena, Cote, Michele L., Zogopoulos, George, Potash, James B., Goes, Fernando S., McCombie, Richard W., Zandi, Peter P., Pirooznia, Mehdi, Kramer, Melissa, Parla, Jennifer, Eshleman, James R., Roberts, Nicholas J., Hruban, Ralph H., Klein, Alison Patricia, and Goggins, Michael

Published
2018

9. The real-time fMRI neurofeedback based stratification of Default Network Regulation Neuroimaging data repository

Author

McDonald, Amalia R., Muraskin, Jordan, Dam, Nicholas T.Van, Froehlich, Caroline, Puccio, Benjamin, Pellman, John, Bauer, Clemens C.C., Akeyson, Alexis, Breland, Melissa M., Calhoun, Vince D., Carter, Steven, Chang, Tiffany P., Gessner, Chelsea, Gianonne, Alyssa, Giavasis, Steven, Glass, Jamie, Homann, Steven, King, Margaret, Kramer, Melissa, Landis, Drew, Lieval, Alexis, Lisinski, Jonathan, Mackay-Brandt, Anna, Miller, Brittny, Panek, Laura, Reed, Hayley, Santiago, Christine, Schoell, Eszter, Sinnig, Richard, Sital, Melissa, Taverna, Elise, Tobe, Russell, Trautman, Kristin, Varghese, Betty, Walden, Lauren, Wang, Runtang, Waters, Abigail B., Wood, Dylan C., Castellanos, F.Xavier, Leventhal, Bennett, Colcombe, Stanley J., LaConte, Stephen, Milham, Michael P., and Craddock, R.Cameron

Published
2017
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11. Long-Read Sequencing Reveals Rapid Evolution of Immunity- and Cancer-Related Genes in Bats.

Author

Scheben, Armin, Ramos, Olivia Mendivil, Kramer, Melissa, Goodwin, Sara, Oppenheim, Sara, Becker, Daniel J, Schatz, Michael C, Simmons, Nancy B, Siepel, Adam, and McCombie, W Richard

Subjects
COMPARATIVE genomics, BATS, MOLECULAR evolution, GENOMICS, GENES, IMMUNE system
Abstract

Bats are exceptional among mammals for their powered flight, extended lifespans, and robust immune systems and therefore have been of particular interest in comparative genomics. Using the Oxford Nanopore Technologies long-read platform, we sequenced the genomes of two bat species with key phylogenetic positions, the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus), and carried out a comprehensive comparative genomic analysis with a diverse collection of bats and other mammals. The high-quality, long-read genome assemblies revealed a contraction of interferon (IFN)-α at the immunity-related type I IFN locus in bats, resulting in a shift in relative IFN-ω and IFN-α copy numbers. Contradicting previous hypotheses of constitutive expression of IFN-α being a feature of the bat immune system, three bat species lost all IFN-α genes. This shift to IFN-ω could contribute to the increased viral tolerance that has made bats a common reservoir for viruses that can be transmitted to humans. Antiviral genes stimulated by type I IFNs also showed evidence of rapid evolution, including a lineage-specific duplication of IFN-induced transmembrane genes and positive selection in IFIT2. In addition, 33 tumor suppressors and 6 DNA-repair genes showed signs of positive selection, perhaps contributing to increased longevity and reduced cancer rates in bats. The robust immune systems of bats rely on both bat-wide and lineage-specific evolution in the immune gene repertoire, suggesting diverse immune strategies. Our study provides new genomic resources for bats and sheds new light on the extraordinary molecular evolution in this critically important group of mammals. [ABSTRACT FROM AUTHOR]

Published
2023
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13. Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A

Author

Sun, Jin-Hua, O'Boyle, II, Donald R., Fridell, Robert A., Langley, David R., Wang, Chunfu, Roberts, Susan B., Nower, Peter, Johnson, Benjamin M., Moulin, Frederic, Nophsker, Michelle J., Wang, Ying-Kai, Liu, Mengping, Rigat, Karen, Tu, Yong, Hewawasam, Piyasena, Kadow, John, Meanwell, Nicholas A., Cockett, Mark, Lemm, Julie A., Kramer, Melissa, and Belema, Makonen

Subjects
Phosphoproteins -- Health aspects, Hepatitis C -- Drug therapy, Drug sensitization -- Methods, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

It is estimated that more than 170 million people are infected with hepatitis C virus (HCV) worldwide (1,2). Clinical trials have demonstrated that, for the first time in human history, [...]

Published
2015

14. A 4-gigabase physical map unlocks the structure and evolution of the complex genome of Aegilops tauschii, the wheat D-genome progenitor

Author

Luo, Ming-Cheng, Gu, Yong Q., You, Frank M., Deal, Karin R., Ma, Yaqin, Hu, Yuqin, Huo, Naxin, Wang, Yi, Wang, Jirui, Chen, Shiyong, Jorgensen, Chad M., Zhang, Yong, McGuire, Patrick E., Pasternak, Shiran, Stein, Joshua C., Ware, Doreen, Kramer, Melissa, McCombie, W. Richard, Kianian, Shahryar F., Martis, Mihaela M., Mayer, Klaus F. X., Sehgal, Sunish K., Li, Wanlong, Gill, Bikram S., Bevan, Michael W., Šimková, Hana, Doležel, Jaroslav, Weining, Song, Lazo, Gerard R., Anderson, Olin D., and Dvorak, Jan

Published
2013

15. The B73 Maize Genome: Complexity, Diversity, and Dynamics

Author

Schnable, Patrick S., Ware, Doreen, Fulton, Robert S., Stein, Joshua C., Wei, Fusheng, Pasternak, Shiran, Liang, Chengzhi, Zhang, Jianwei, Fulton, Lucinda, Graves, Tina A., Minx, Patrick, Reily, Amy Denise, Courtney, Laura, Kruchowski, Scott S., Tomlinson, Chad, Strong, Cindy, Delehaunty, Kim, Fronick, Catrina, Courtney, Bill, Rock, Susan M., Belter, Eddie, Du, Feiyu, Kim, Kyung, Abbott, Rachel M., Cotton, Marc, Levy, Andy, Marchetto, Pamela, Ochoa, Kerri, Jackson, Stephanie M., Gillam, Barbara, Chen, Weizu, Yan, Le, Higginbotham, Jamey, Cardenas, Marco, Waligorski, Jason, Applebaum, Elizabeth, Phelps, Lindsey, Falcone, Jason, Kanchi, Krishna, Thane, Thynn, Scimone, Adam, Thane, Nay, Henke, Jessica, Wang, Tom, Ruppert, Jessica, Shah, Neha, Rotter, Kelsi, Hodges, Jennifer, Ingenthron, Elizabeth, Cordes, Matt, Kohlberg, Sara, Sgro, Jennifer, Delgado, Brandon, Mead, Kelly, Chinwalla, Asif, Leonard, Shawn, Crouse, Kevin, Collura, Kristi, Kudrna, Dave, Currie, Jennifer, He, Ruifeng, Angelova, Angelina, Rajasekar, Shanmugam, Mueller, Teri, Lomeli, Rene, Scara, Gabriel, Ko, Ara, Delaney, Krista, Wissotski, Marina, Lopez, Georgina, Campos, David, Braidotti, Michele, Ashley, Elizabeth, Golser, Wolfgang, Kim, HyeRan, Lee, Seunghee, Lin, Jinke, Dujmic, Zeljko, Kim, Woojin, Talag, Jayson, Zuccolo, Andrea, Fan, Chuanzhu, Sebastian, Aswathy, Kramer, Melissa, Spiegel, Lori, Nascimento, Lidia, Zutavern, Theresa, Miller, Beth, Ambroise, Claude, Muller, Stephanie, Spooner, Will, Narechania, Apurva, Ren, Liya, Wei, Sharon, Kumari, Sunita, Faga, Ben, Levy, Michael J., McMahan, Linda, Van Buren, Peter, Vaughn, Matthew W., Ying, Kai, Yeh, Cheng-Ting, Emrich, Scott J., Jia, Yi, Kalyanaraman, Ananth, Hsia, An-Ping, Barbazuk, W. Brad, Baucom, Regina S., Brutnell, Thomas P., Carpita, Nicholas C., Chaparro, Cristian, Chia, Jer-Ming, Deragon, Jean-Marc, Estill, James C., Fu, Yan, Jeddeloh, Jeffrey A., Han, Yujun, Lee, Hyeran, Li, Pinghua, Lisch, Damon R., Liu, Sanzhen, Liu, Zhijie, Nagel, Dawn Holligan, McCann, Maureen C., SanMiguel, Phillip, Myers, Alan M., Nettleton, Dan, Nguyen, John, Penning, Bryan W., Ponnala, Lalit, Schneider, Kevin L., Schwartz, David C., Sharma, Anupma, Soderlund, Carol, Springer, Nathan M., Sun, Qi, Wang, Hao, Waterman, Michael, Westerman, Richard, Wolfgruber, Thomas K., Yang, Lixing, Yu, Yeisoo, Zhang, Lifang, Zhou, Shiguo, Zhu, Qihui, Bennetzen, Jeffrey L., Dawe, R. Kelly, Jiang, Jiming, Jiang, Ning, Presting, Gernot G., Wessler, Susan R., Aluru, Srinivas, Martienssen, Robert A., Clifton, Sandra W., McCombie, W. Richard, Wing, Rod A., and Wilson, Richard K.

Published
2009
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17. Development of BET inhibitors as potential treatments for cancer: A new carboline chemotype

Author

Hill, Matthew D., Quesnelle, Claude, Tokarski, John, Fang, Haiquan, Fanslau, Carolynn, Haarhoff, Zuzana, Kramer, Melissa, Madari, Shilpa, Wiebesiek, Amy, Morrison, John, Simmermacher-Mayer, Jean, Sinz, Michael, Westhouse, Richard, Xie, Chunshan, Zhao, Jiuqiao, Huang, Lisa, Sheriff, Steven, Yan, Chunhong, Marsilio, Frank, Everlof, Gerry, Zvyaga, Tatyana, Lee, Francis, Gavai, Ashvinikumar V., and Degnan, Andrew P.

Published
2021
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18. Exome Sequencing of Familial Bipolar Disorder

Author

Goes, Fernando S., Pirooznia, Mehdi, Parla, Jennifer S., Kramer, Melissa, Ghiban, Elena, Mavruk, Senem, Chen, Yun-Ching, Monson, Eric T., Willour, Virginia L., Karchin, Rachel, Flickinger, Matthew, Locke, Adam E., Levy, Shawn E., Scott, Laura J., Boehnke, Michael, Stahl, Eli, Moran, Jennifer L., Hultman, Christina M., Landén, Mikael, Purcell, Shaun M., Sklar, Pamela, Zandi, Peter P., McCombie, W. Richard, and Potash, James B.

Published
2016
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19. Development of BET inhibitors as potential treatments for cancer: A search for structural diversity

Author

Hill, Matthew D., Fang, Haiquan, Tokarski, John, Fanslau, Carolynn, Haarhoff, Zuzana, Huang, Christine, Kramer, Melissa, Menard, Krista, Monereau, Laura, Morrison, John, Ranasinghe, Asoka, Shields, Eric E., Tye, Ching Kim, Westhouse, Richard, Everlof, Gerry, Sheriff, Steven, Yan, Chunhong, Marsilio, Frank, Zhang, Lisa, Zvyaga, Tatyana, Lee, Francis, Gavai, Ashvinikumar V., and Degnan, Andrew P.

Published
2021
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21. Analysis of the bread wheat genome using whole-genome shotgun sequencing

Author

Brenchley, Rachel, Spannagl, Manuel, Pfeifer, Matthias, Barker, Gary L.A., D'Amore, Rosalinda, Allen, Alexandra M., McKenzie, Neil, Kramer, Melissa, Kerhornou, Arnaud, Bolser, Dan, Kay, Suzanne, Waite, Darren, Trick, Martin, Bancroft, Ian, Gu, Yong, Huo, Naxin, Luo, Ming-Cheng, Sehgal, Sunish, Gill, Bikram, Kianian, Sharyar, Anderson, Olin, Kersey, Paul, Dvorak, Jan, McCombie, W. Richard, Hall, Anthony, Mayer, Klaus F.X., Edwards, Keith J., Bevan, Michael W., and Hall, Neil

Subjects
Plant genetics -- Research -- Physiological aspects -- Genetic aspects, Wheat -- Physiological aspects -- Genetic aspects -- Research, Genomics -- Research -- Physiological aspects -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Bread wheat (Triticum aestivum) is a globally important crop, accounting for 20 per cent of the calories consumed by humans. Major efforts are underway worldwide to increase wheat production by extending genetic diversity and analysing key traits, and genomic resources can accelerate progress. But so far the very large size and polyploid complexity of the bread wheat genome have been substantial barriers to genome analysis. Here we report the sequencing of its large, 17-gigabase-pair, hexaploid genome using 454pyrosequencing, and comparison of this with the sequences of diploid ancestral and progenitor genomes. We identified between 94,000 and 96,000 genes, and assigned two-thirds to the three component genomes (A, B and D) of hexaploid wheat. High-resolution synteny maps identified many small disruptions to conserved gene order. We show that the hexaploid genome is highly dynamic, with significant loss of gene family members on polyploidization and domestication, and an abundance of gene fragments. Several classes of genes involved in energy harvesting, metabolism and growth are among expanded gene families that could be associated with crop productivity. Our analyses, coupled with the identification of extensive genetic variation, provide a resource for accelerating gene discovery and improving this major crop., With a global output of 681 million tonnes in 2011 (1), bread wheat accounts for 20% of the calories consumed by humans (2) and is an important source of protein, [...]

Published
2012
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23. Development of BET Inhibitors as Potential Treatments for Cancer: Optimization of Pharmacokinetic Properties.

Author

Hill, Matthew D., Fang, Haiquan, Norris, Derek, Delucca, George V., Huang, Hong, DeBenedetto, Mikkel, Quesnelle, Claude, Schmitz, William D., Tokarski, John S., Sheriff, Steven, Yan, Chunhong, Fanslau, Caroline, Haarhoff, Zuzana, Huang, Christine, Kramer, Melissa, Madari, Shilpa, Menard, Krista, Monereau, Laura, Morrison, John, and Raghavan, Nirmala

Published
2022
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25. The tomato genome sequence provides insights into fleshy fruit evolution

Author

Sato, Shusei, Tabata, Satoshi, Hirakawa, Hideki, Asamizu, Erika, Shirasawa, Kenta, Isobe, Sachiko, Kaneko, Takakazu, Nakamura, Yasukazu, Shibata, Daisuke, Aoki, Koh, Egholm, Michael, Knight, James, Bogden, Robert, Li, Changbao, Shuang, Yang, Xu, Xun, Pan, Shengkai, Cheng, Shifeng, Liu, Xin, Ren, Yuanyuan, Wang, Jun, Albiero, Alessandro, Dal Pero, Francesca, Todesco, Sara, Van Eck, Joyce, Buels, Robert M., Bombarely, Aureliano, Gosselin, Joseph R., Huang, Minyun, Leto, Jonathan A., Menda, Naama, Strickler, Susan, Mao, Linyong, Gao, Shan, Tecle, Isaak Y., York, Thomas, Zheng, Yi, Vrebalov, Julia T., Lee, JeMin, Zhong, Silin, Mueller, Lukas A., Stiekema, Willem J., Ribeca, Paolo, Alioto, Tyler, Yang, Wencai, Huang, Sanwen, Du, Yongchen, Zhang, Zhonghua, Gao, Jianchang, Guo, Yanmei, Wang, Xiaoxuan, Li, Ying, He, Jun, Li, Chuanyou, Cheng, Zhukuan, Zuo, Jianru, Ren, Jianfeng, Zhao, Jiuhai, Yan, Liuhua, Jiang, Hongling, Wang, Bao, Li, Hongshuang, Li, Zhenjun, Fu, Fuyou, Chen, Bingtang, Han, Bin, Feng, Qi, Fan, Danlin, Wang, Ying, Ling, Hongqing, Xue, Yongbiao, Ware, Doreen, Richard McCombie, W., Lippman, Zachary B., Chia, Jer-Ming, Jiang, Ke, Pasternak, Shiran, Gelley, Laura, Kramer, Melissa, Anderson, Lorinda K., Chang, Song-Bin, Royer, Suzanne M., Shearer, Lindsay A., Stack, Stephen M., Rose, Jocelyn K. C., Xu, Yimin, Eannetta, Nancy, Matas, Antonio J., McQuinn, Ryan, Tanksley, Steven D., Camara, Francisco, Guigó, Roderic, Rombauts, Stephane, Fawcett, Jeffrey, Van de Peer, Yves, Zamir, Dani, Liang, Chunbo, Spannagl, Manuel, Gundlach, Heidrun, Bruggmann, Remy, Mayer, Klaus, Jia, Zhiqi, Zhang, Junhong, Ye, Zhibiao, Bishop, Gerard J., Butcher, Sarah, Lopez-Cobollo, Rosa, Buchan, Daniel, Filippis, Ioannis, Abbott, James, Dixit, Rekha, Singh, Manju, Singh, Archana, Kumar Pal, Jitendra, Pandit, Awadhesh, Kumar Singh, Pradeep, Kumar Mahato, Ajay, Dogra, Vivek, Gaikwad, Kishor, Raj Sharma, Tilak, Mohapatra, Trilochan, Kumar Singh, Nagendra, Causse, Mathilde, Rothan, Christophe, Schiex, Thomas, Noirot, Céline, Bellec, Arnaud, Klopp, Christophe, Delalande, Corinne, Berges, Hélène, Mariette, Jérôme, Frasse, Pierre, Vautrin, Sonia, Zouine, Mohamed, Latché, Alain, Rousseau, Christine, Regad, Farid, Pech, Jean-Claude, Philippot, Murielle, Bouzayen, Mondher, Pericard, Pierre, Osorio, Sonia, Fernandez del Carmen, Asunción, Monforte, Antonio, Granell, Antonio, Fernandez-Muñoz, Rafael, Conte, Mariana, Lichtenstein, Gabriel, Carrari, Fernando, De Bellis, Gianluca, Fuligni, Fabio, Peano, Clelia, Grandillo, Silvana, Termolino, Pasquale, Pietrella, Marco, Fantini, Elio, Falcone, Giulia, Fiore, Alessia, Giuliano, Giovanni, Lopez, Loredana, Facella, Paolo, Perrotta, Gaetano, Daddiego, Loretta, Bryan, Glenn, Orozco, Modesto, Pastor, Xavier, Torrents, David, van Schriek, Marco G. M., Feron, Richard M.C., van Oeveren, Jan, de Heer, Peter, daPonte, Lorena, Jacobs-Oomen, Saskia, Cariaso, Mike, Prins, Marcel, van Eijk, Michiel J. T., Janssen, Antoine, van Haaren, Mark J. J., Jo, Sung-Hwan, Kim, Jungeun, Kwon, Suk-Yoon, Kim, Sangmi, Koo, Dal-Hoe, Lee, Sanghyeob, Hur, Cheol-Goo, Clouser, Christopher, Rico, Alain, Hallab, Asis, Gebhardt, Christiane, Klee, Kathrin, Jöcker, Anika, Warfsmann, Jens, Göbel, Ulrike, Kawamura, Shingo, Yano, Kentaro, Sherman, Jamie D., Fukuoka, Hiroyuki, Negoro, Satomi, Bhutty, Sarita, Chowdhury, Parul, Chattopadhyay, Debasis, Datema, Erwin, Smit, Sandra, Schijlen, Elio G. W. M., van de Belt, Jose, van Haarst, Jan C., Peters, Sander A., van Staveren, Marjo J., Henkens, Marleen H. C., Mooyman, Paul J. W., Hesselink, Thamara, van Ham, Roeland C. H. J., Jiang, Guoyong, Droege, Marcus, Choi, Doil, Kang, Byung-Cheol, Dong Kim, Byung, Park, Minkyu, Kim, Seungill, Yeom, Seon-In, Lee, Yong-Hwan, Choi, Yang-Do, Li, Guangcun, Gao, Jianwei, Liu, Yongsheng, Huang, Shengxiong, Fernandez-Pedrosa, Victoria, Collado, Carmen, Zuñiga, Sheila, Wang, Guoping, Cade, Rebecca, Dietrich, Robert A., Rogers, Jane, Knapp, Sandra, Fei, Zhangjun, White, Ruth A., Thannhauser, Theodore W., Giovannoni, James J., Angel Botella, Miguel, Gilbert, Louise, Gonzalez, Ramon, Luis Goicoechea, Jose, Yu, Yeisoo, Kudrna, David, Collura, Kristi, Wissotski, Marina, Wing, Rod, Schoof, Heiko, Meyers, Blake C., Bala Gurazada, Aishwarya, Green, Pamela J., Mathur, Saloni, Vyas, Shailendra, Solanke, Amolkumar U., Kumar, Rahul, Gupta, Vikrant, Sharma, Arun K., Khurana, Paramjit, Khurana, Jitendra P., Tyagi, Akhilesh K., Dalmay, Tamas, Mohorianu, Irina, Walts, Brandon, Chamala, Srikar, Brad Barbazuk, W., Li, Jingping, Guo, Hui, Lee, Tae-Ho, Wang, Yupeng, Zhang, Dong, Paterson, Andrew H., Wang, Xiyin, Tang, Haibao, Barone, Amalia, Luisa Chiusano, Maria, Raffaella Ercolano, Maria, D’Agostino, Nunzio, Di Filippo, Miriam, Traini, Alessandra, Sanseverino, Walter, Frusciante, Luigi, Seymour, Graham B., Elharam, Mounir, Fu, Ying, Hua, Axin, Kenton, Steven, Lewis, Jennifer, Lin, Shaoping, Najar, Fares, Lai, Hongshing, Qin, Baifang, Qu, Chunmei, Shi, Ruihua, White, Douglas, White, James, Xing, Yanbo, Yang, Keqin, Yi, Jing, Yao, Ziyun, Zhou, Liping, Roe, Bruce A., Vezzi, Alessandro, D’Angelo, Michela, Zimbello, Rosanna, Schiavon, Riccardo, Caniato, Elisa, Rigobello, Chiara, Campagna, Davide, Vitulo, Nicola, Valle, Giorgio, Nelson, David R., De Paoli, Emanuele, Szinay, Dora, de Jong, Hans H., Bai, Yuling, Visser, Richard G. F., Klein Lankhorst, René M., Beasley, Helen, McLaren, Karen, Nicholson, Christine, Riddle, Claire, and Gianese, Giulio

Published
2012
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30. The Rice Annotation Project Database (RAP-DB): 2008 update*

Author

Tanaka, Tsuyoshi, Antonio, Baltazar A., Kikuchi, Shoshi, Matsumoto, Takashi, Nagamura, Yoshiaki, Numa, Hisataka, Sakai, Hiroaki, Wu, Jianzhong, Itoh, Takeshi, Sasaki, Takuji, Aono, Ryo, Fujii, Yasuyuki, Habara, Takuya, Harada, Erimi, Kanno, Masako, Kawahara, Yoshihiro, Kawashima, Hiroaki, Kubooka, Hiromi, Matsuya, Akihiro, Nakaoka, Hajime, Saichi, Naomi, Sanbonmatsu, Ryoko, Sato, Yoshiharu, Shinso, Yuji, Suzuki, Mami, Takeda, Jun-ichi, Tanino, Motohiko, Todokoro, Fusano, Yamaguchi, Kaori, Yamamoto, Naoyuki, Yamasaki, Chisato, Imanishi, Tadashi, Okido, Toshihisa, Tada, Masahito, Ikeo, Kazuho, Tateno, Yoshio, Gojobori, Takashi, Lin, Yao-Cheng, Wei, Fu-Jin, Hsing, Yue-ie, Zhao, Qiang, Han, Bin, Kramer, Melissa R., McCombie, Richard W., Lonsdale, David, O’Donovan, Claire C., Whitfield, Eleanor J., Apweiler, Rolf, Koyanagi, Kanako O., Khurana, Jitendra P., Raghuvanshi, Saurabh, Singh, Nagendra K., Tyagi, Akhilesh K., Haberer, Georg, Fujisawa, Masaki, Hosokawa, Satomi, Ito, Yukiyo, Ikawa, Hiroshi, Shibata, Michie, Yamamoto, Mayu, Bruskiewich, Richard M., Hoen, Douglas R., Bureau, Thomas E., Namiki, Nobukazu, Ohyanagi, Hajime, Sakai, Yasumichi, Nobushima, Satoshi, Sakata, Katsumi, Barrero, Roberto A., Sato, Yutaka, Souvorov, Alexandre, Smith-White, Brian, Tatusova, Tatiana, An, Suyoung, An, Gynheung, OOta, Satoshi, Fuks, Galina, Messing, Joachim, Christie, Karen R., Lieberherr, Damien, Kim, HyeRan, Zuccolo, Andrea, Wing, Rod A., Nobuta, Kan, Green, Pamela J., Lu, Cheng, Meyers, Blake C., Chaparro, Cristian, Piegu, Benoit, Panaud, Olivier, and Echeverria, Manuel

Published
2008

31. Establishing the baseline level of repetitive element expression in the human cortex

Author

Kramer Melissa, Parla Jennifer, McCombie W, Yolken Robert H, Tyekucheva Svitlana, Wheelan Sarah J, and Sabunciyan Sarven

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Although nearly half of the human genome is comprised of repetitive sequences, the expression profile of these elements remains largely uncharacterized. Recently developed high throughput sequencing technologies provide us with a powerful new set of tools to study repeat elements. Hence, we performed whole transcriptome sequencing to investigate the expression of repetitive elements in human frontal cortex using postmortem tissue obtained from the Stanley Medical Research Institute. Results We found a significant amount of reads from the human frontal cortex originate from repeat elements. We also noticed that Alu elements were expressed at levels higher than expected by random or background transcription. In contrast, L1 elements were expressed at lower than expected amounts. Conclusions Repetitive elements are expressed abundantly in the human brain. This expression pattern appears to be element specific and can not be explained by random or background transcription. These results demonstrate that our knowledge about repetitive elements is far from complete. Further characterization is required to determine the mechanism, the control, and the effects of repeat element expression.

Published
2011
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32. Multiple-infection and recombination in HIV-1 within a longitudinal cohort of women

Author

Templeton Alan R, Kramer Melissa G, Jarvis Joseph, Kowalski Jeanne, Gange Stephen, Schneider Michael F, Shao Qiujia, Zhang Guang, Yeh Mei-Fen, Tsai Hua-Ling, Zhang Hong, and Markham Richard B

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Recombination between strains of HIV-1 only occurs in individuals with multiple infections, and the incidence of recombinant forms implies that multiple infection is common. Most direct studies indicate that multiple infection is rare. We determined the rate of multiple infection in a longitudinal study of 58 HIV-1 positive participants from The Women's Interagency HIV Study with a richer sampling design than previous direct studies, and we investigated the role of recombination and sampling design on estimating the multiple infection rate. Results 40% of our sample had multiple HIV-1 infections. This rate of multiple infection is statistically consistent with previous studies once differences in sampling design are taken into account. Injection drug use significantly increased the incidence of multiple infections. In general there was rapid elimination of secondary strains to undetectable levels, but in 3 cases a superinfecting strain displaced the initial infecting strain and in two cases the strains coexisted throughout the study. All but one secondary strain was detected as an inter- and/or intra-genic recombinant. Injection drug use significantly increased the rate of observed recombinants. Conclusion Our multiple infection rate is consistent with rates estimated from the frequency of recombinant forms of HIV-1. The fact that our results are also consistent with previous direct studies that had reported a much lower rate illustrates the critical role of sampling design in estimating this rate. Multiple infection and recombination significantly add to the genetic diversity of HIV-1 and its evolutionary potential, and injection drug use significantly increases both.

Published
2009
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33. Almost airborne

Author

Kramer, Melissa G. and Marden, James H.

Published
1997

34. Functionalized triazines as potent HCV entry inhibitors

Author

Mull, Eric S., Sun, Li-Qiang, Zhao, Qian, Eggers, Betsy, Pokornowski, Kevin, Zhai, Guangzhi, Rajamani, Ramkumar, Jenkins, Susan, Kramer, Melissa, Wang, Ying-Kai, Fang, Hua, Tenney, Daniel, Baldick, Carl J., Cockett, Mark I., Meanwell, Nicholas A., and Scola, Paul M.

Published
2017
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36. Deciphering the genome structure and paleohistory of _Theobroma cacao_

Author

Chaparro, Cristian, Murat, Florent, Carlson, John, Guignon, Valentin, Tahi, Mathias, Guiderdoni, Emmanuel, Legavre, Thierry, Fouet, Olivier, Sallet, Erika, Sabau, Xavier, Akaza, Joseph Moroh, Quetier, Francis, Guiltinan, Mark, Poulain, Julie, T., Schiex, Axtell, Michael, Pitollat, Bertrand, Panaud, Olivier, Maximova, Siela, Ruiz, Manuel, Dievart, Anne, Ma, Zhaorong, Gramacho, Karina, Wincker, Patrick, Roguet, Yolande, Kramer, Melissa, Zhang, Yufan, D’Hont, Angélique, Sidibe-Bocs, Stephanie, Lanaud, Claire, Argout, Xavier, Rodier-Goud, Maguy, Gelley, Laura, Brown, Spencer, Brunel, Dominique, Infante, Diogenes, Salse, Jerome, Barbosa-Neto, Jose Fernandes, Sh, Zi, Bourge, Mickael, Golser, Wolfgang, Kebe, Ismael, Aury, Jean Marc, Sabot, Francois, Bérard, Aurélie, Viot, Christopher, Song, Xiang, Costet, Pierre, Droc, Gaetan, Kudrna, Dave, Ammiraju, Jetty Siva, Boccara, Michel, Clement, Didier, Wing, Rod, Gouzy, Jerome, Abrouk, Michael, Schuster, Stephan, Risterucci, Ange Marie, Rivalan, Ronan, McCombie, W. Richard, and Allegre, Mathilde

Published
2010
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37. The Combination of Rapamycin and Resveratrol Blocks Autophagy and Induces Apoptosis in Breast Cancer Cells

Author

Alayev, Anya, Berger, Sara Malka, Kramer, Melissa Y., Schwartz, Naomi S., and Holz, Marina K.

Subjects
Sirolimus, Ribosomal Protein S6 Kinases, TOR Serine-Threonine Kinases, Estrogen Receptor alpha, Apoptosis, Breast Neoplasms, Drug Synergism, Mechanistic Target of Rapamycin Complex 1, Models, Biological, Article, Up-Regulation, Resveratrol, Cell Line, Tumor, Multiprotein Complexes, Stilbenes, Autophagy, Humans, Female, biological phenomena, cell phenomena, and immunity, Proto-Oncogene Proteins c-akt, Cell Proliferation, Signal Transduction
Abstract

Hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) is a frequent event in breast cancer and current efforts are aimed at targeting the mTORC1 signaling pathway in combination with other targeted therapies. However, patients often develop drug resistance in part due to activation of the oncogenic Akt signaling and upregulation of autophagy, which protects cancer cells from apoptosis. In the present study we investigated the effects of combination therapy of rapamycin (an allosteric mTORC1 inhibitor) together with resveratrol (a phytoestrogen that inhibits autophagy). Our results show that combination of these drugs maintains inhibition of mTORC1 signaling, while preventing upregulation of Akt activation and autophagy, causing apoptosis. Additionally, this combination was effective in estrogen receptor positive and negative breast cancer cells, underscoring its versatility.

Published
2015

44. Comprehensive evaluation of liver microsomal cytochrome P450 3A (CYP3A) inhibition: comparison of cynomolgus monkey and human.

Author

Haarhoff, Zuzana E., Kramer, Melissa A., Zvyaga, Tatyana A., Zhang, Jun, Bhutani, Priyadeep, Subramanian, Murali, and Rodrigues, A. David

Subjects
*LIVER microsomes, *CYTOCHROME P-450, *KRA, *RALOXIFENE, *AMINO acids, *PHYSIOLOGY
Abstract

1. Members of the cytochrome P450 3A (CYP3A) subfamily metabolize numerous compounds and serve as the loci of drug–drug interactions (DDIs). Because of high amino acid sequence identity with human CYP3A, the cynomolgus monkey has been proposed as a model species to support DDI risk assessment. 2. Therefore, the objective of this study was to evaluate 35 known inhibitors of human CYP3A using human (HLM) and cynomolgus monkey (CLM) liver microsomes. Midazolam was employed as substrate to generate IC50values (concentration of inhibitor rendering 50% inhibition) in the absence and presence of a preincubation (30 mins) with NADPH. 3. In the absence of preincubation, the IC50values generated with CLM were similar to those obtained with HLM (86% within 2-fold; 100% within 3-fold difference). However, significant differences (up to 48-fold) in preincubation IC50were observed with 17% of the compounds (raloxifene, bergamottin, nicardipine, mibefradil, ritonavir, and diltiazem). 4. Our results indicate that in most cases the cynomolgus monkey can be a viable DDI model. However, significant species differences in time-dependent CYP3A inhibition can be observed for some compounds. In the case of raloxifene, such a difference can be ascribed to a specific CYP3A4 amino acid residue. [ABSTRACT FROM PUBLISHER]

Published
2017
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47. Validation and assessment of variant calling pipelines for next-generation sequencing.

Author

Pirooznia, Mehdi Pirooznia, Kramer, Melissa, Parla, Jennifer, Goes, Fernando S, Potash, James B, McCombie, W Richard, and Zandi, Peter P

Abstract

Background: The processing and analysis of the large scale data generated by next-generation sequencing (NGS) experiments is challenging and is a burgeoning area of new methods development. Several new bioinformatics tools have been developed for calling sequence variants from NGS data. Here, we validate the variant calling of these tools and compare their relative accuracy to determine which data processing pipeline is optimal. Results: We developed a unified pipeline for processing NGS data that encompasses four modules: mapping, filtering, realignment and recalibration, and variant calling. We processed 130 subjects from an ongoing whole exome sequencing study through this pipeline. To evaluate the accuracy of each module, we conducted a series of comparisons between the single nucleotide variant (SNV) calls from the NGS data and either gold-standard Sanger sequencing on a total of 700 variants or array genotyping data on a total of 9,935 single-nucleotide polymorphisms. A head to head comparison showed that Genome Analysis Toolkit (GATK) provided more accurate calls than SAMtools (positive predictive value of 92.55% vs. 80.35%, respectively). Realignment of mapped reads and recalibration of base quality scores before SNV calling proved to be crucial to accurate variant calling. GATK HaplotypeCaller algorithm for variant calling outperformed the UnifiedGenotype algorithm. We also showed a relationship between mapping quality, read depth and allele balance, and SNV call accuracy. However, if best practices are used in data processing, then additional filtering based on these metrics provides little gains and accuracies of >99% are achievable. Conclusions: Our findings will help to determine the best approach for processing NGS data to confidently call variants for downstream analyses. To enable others to implement and replicate our results, all of our codes are freely available at http://metamoodics.org/wes. [ABSTRACT FROM AUTHOR]

Published
2014
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48. A 4-gigabase physical map unlocks the structure and evolution of the complex genome of Aegilops tauschii, the wheat D-genome progenitor.

Author

Ming-Cheng Luo, Yong Q. Gu, Frank M. You, Karin R. Deal, Yaqin Ma, Yuqin Hu, Naxin Huo, Yi Wang, Jirui Wang, Shiyong Chen, Jorgensen, Chad M., Yong Zhang, McGuire, Patrick E., Pasternak, Shiran, Stein, Joshua C., Ware, Doreen, Kramer, Melissa, McCombie, W. Richard, Kianian, Shahryar F., and Martis, Mihaela M.

Subjects
AEGILOPS, PROGENITOR cells, GENE mapping, GENETIC markers, BRACHYPODIUM
Abstract

The current limitations in genome sequencing technology require the construction of physical maps for high-quality draft sequences of large plant genomes, such as that of Aegilops tauschii, the wheat D-genome progenitor. To construct a physical map of the Ae. tauschii genome, we fingerprinted 461,706 bacterial artificial chromosome clones, assembled contigs, designed a 10K Ae. tauschii Infinium SNP array, constructed a 7,185-marker genetic map, and anchored on the map contigs totaling 4.03 Gb. Using whole genome shotgun reads, we extended the SNP marker sequences and found 17,093 genes and gene fragments. We showed that collinearity of the Ae. tauschii genes with Brachypodium distachyon, rice, and sorghum decreased with phylogenetic distance and that structural genome evolution rates have been high across all investigated lineages in subfamily Pooideae, including that of Brachypodieae. We obtained additional information about the evolution of the seven Triticeae chromosomes from 12 ancestral chromosomes and uncovered a pattern of centromere inactivation accompanying nested chromosome insertions in grasses. We showed that the density of noncollinear genes along the Ae. tauschii chromosomes positively correlates with recombination rates, suggested a cause, and showed that new genes, exemplified by disease resistance genes, are preferentially located in high-recombination chromosome regions. [ABSTRACT FROM AUTHOR]

Published
2013
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49. A Hybrid Likelihood Model for Sequence-Based Disease Association Studies.

Author

Yun-Ching Chen, Carter, Hannah, Parla, Jennifer, Kramer, Melissa, Goes, Fernando S., Pirooznia, Mehdi, Zandi, Peter P., McCombie, W. Richard, Potash, James B., and Karchin, Rachel

Abstract

In the past few years, case-control studies of common diseases have shifted their focus from single genes to whole exomes. New sequencing technologies now routinely detect hundreds of thousands of sequence variants in a single study, many of which are rare or even novel. The limitation of classical single-marker association analysis for rare variants has been a challenge in such studies. A new generation of statistical methods for case-control association studies has been developed to meet this challenge. A common approach to association analysis of rare variants is the burden-style collapsing methods to combine rare variant data within individuals across or within genes. Here, we propose a new hybrid likelihood model that combines a burden test with a test of the position distribution of variants. In extensive simulations and on empirical data from the Dallas Heart Study, the new model demonstrates consistently good power, in particular when applied to a gene set (e.g., multiple candidate genes with shared biological function or pathway), when rare variants cluster in key functional regions of a gene, and when protective variants are present. When applied to data from an ongoing sequencing study of bipolar disorder (191 cases, 107 controls), the model identifies seven gene sets with nominal p-values <0.05, of which one MAPK signaling pathway (KEGG) reaches trend-level significance after correcting for multiple testing. [ABSTRACT FROM AUTHOR]

Published
2013
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