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1. Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element

Author

Wilson Leung, Christopher D. Shaffer, Elizabeth J. Chen, Thomas J. Quisenberry, Kevin Ko, John M. Braverman, Thomas C. Giarla, Nathan T. Mortimer, Laura K. Reed, Sheryl T. Smith, Srebrenka Robic, Shannon R. McCartha, Danielle R. Perry, Lindsay M. Prescod, Zenyth A. Sheppard, Ken J. Saville, Allison McClish, Emily A. Morlock, Victoria R. Sochor, Brittney Stanton, Isaac C. Veysey-White, Dennis Revie, Luis A. Jimenez, Jennifer J. Palomino, Melissa D. Patao, Shane M. Patao, Edward T. Himelblau, Jaclyn D. Campbell, Alexandra L. Hertz, Maddison F. McEvilly, Allison R. Wagner, James Youngblom, Baljit Bedi, Jeffery Bettincourt, Erin Duso, Maiye Her, William Hilton, Samantha House, Masud Karimi, Kevin Kumimoto, Rebekah Lee, Darryl Lopez, George Odisho, Ricky Prasad, Holly Lyn Robbins, Tanveer Sandhu, Tracy Selfridge, Kara Tsukashima, Hani Yosif, Nighat P. Kokan, Latia Britt, Alycia Zoellner, Eric P. Spana, Ben T. Chlebina, Insun Chong, Harrison Friedman, Danny A. Mammo, Chun L. Ng, Vinayak S. Nikam, Nicholas U. Schwartz, Thomas Q. Xu, Martin G. Burg, Spencer M. Batten, Lindsay M. Corbeill, Erica Enoch, Jesse J. Ensign, Mary E. Franks, Breanna Haiker, Judith A. Ingles, Lyndsay D. Kirkland, Joshua M. Lorenz-Guertin, Jordan Matthews, Cody M. Mittig, Nicholaus Monsma, Katherine J. Olson, Guillermo Perez-Aragon, Alen Ramic, Jordan R. Ramirez, Christopher Scheiber, Patrick A. Schneider, Devon E. Schultz, Matthew Simon, Eric Spencer, Adam C. Wernette, Maxine E. Wykle, Elizabeth Zavala-Arellano, Mitchell J. McDonald, Kristine Ostby, Peter Wendland, Justin R. DiAngelo, Alexis M. Ceasrine, Amanda H. Cox, James E.B. Docherty, Robert M. Gingras, Stephanie M. Grieb, Michael J. Pavia, Casey L. Personius, Grzegorz L. Polak, Dale L. Beach, Heaven L. Cerritos, Edward A. Horansky, Karim A. Sharif, Ryan Moran, Susan Parrish, Kirsten Bickford, Jennifer Bland, Juliana Broussard, Kerry Campbell, Katelynn E. Deibel, Richard Forka, Monika C. Lemke, Marlee B. Nelson, Catherine O'Keeffe, S. Mariel Ramey, Luke Schmidt, Paola Villegas, Christopher J. Jones, Stephanie L. Christ, Sami Mamari, Adam S. Rinaldi, Ghazal Stity, Amy T. Hark, Mark Scheuerman, S. Catherine Silver Key, Briana D. McRae, Adam S. Haberman, Sam Asinof, Harriette Carrington, Kelly Drumm, Terrance Embry, Richard McGuire, Drew Miller-Foreman, Stella Rosen, Nadia Safa, Darrin Schultz, Matt Segal, Yakov Shevin, Petros Svoronos, Tam Vuong, Gary Skuse, Don W. Paetkau, Rachael K. Bridgman, Charlotte M. Brown, Alicia R. Carroll, Francesca M. Gifford, Julie Beth Gillespie, Susan E. Herman, Krystal L. Holtcamp, Misha A. Host, Gabrielle Hussey, Danielle M. Kramer, Joan Q. Lawrence, Madeline M. Martin, Ellen N. Niemiec, Ashleigh P. O'Reilly, Olivia A. Pahl, Guadalupe Quintana, Elizabeth A.S. Rettie, Torie L. Richardson, Arianne E. Rodriguez, Mona O. Rodriguez, Laura Schiraldi, Joanna J. Smith, Kelsey F. Sugrue, Lindsey J. Suriano, Kaitlyn E. Takach, Arielle M. Vasquez, Ximena Velez, Elizabeth J. Villafuerte, Laura T. Vives, Victoria R. Zellmer, Jeanette Hauke, Charles R. Hauser, Karolyn Barker, Laurie Cannon, Perouza Parsamian, Samantha Parsons, Zachariah Wichman, Christopher W. Bazinet, Diana E. Johnson, Abubakarr Bangura, Jordan A. Black, Victoria Chevee, Sarah A. Einsteen, Sarah K. Hilton, Max Kollmer, Rahul Nadendla, Joyce Stamm, Antoinette E. Fafara-Thompson, Amber M. Gygi, Emmy E. Ogawa, Matt Van Camp, Zuzana Kocsisova, Judith L. Leatherman, Cassie M. Modahl, Michael R. Rubin, Susana S. Apiz-Saab, Suzette M. Arias-Mejias, Carlos F. Carrion-Ortiz, Patricia N. Claudio-Vazquez, Debbie M. Espada-Green, Marium Feliciano-Camacho, Karina M. Gonzalez-Bonilla, Mariela Taboas-Arroyo, Dorianmarie Vargas-Franco, Raquel Montañez-Gonzalez, Joseph Perez-Otero, Myrielis Rivera-Burgos, Francisco J. Rivera-Rosario, Heather L. Eisler, Jackie Alexander, Samatha K. Begley, Deana Gabbard, Robert J. Allen, Wint Yan Aung, William D. Barshop, Amanda Boozalis, Vanessa P. Chu, Jeremy S. Davis, Ryan N. Duggal, Robert Franklin, Katherine Gavinski, Heran Gebreyesus, Henry Z. Gong, Rachel A. Greenstein, Averill D. Guo, Casey Hanson, Kaitlin E. Homa, Simon C. Hsu, Yi Huang, Lucy Huo, Sarah Jacobs, Sasha Jia, Kyle L. Jung, Sarah Wai-Chee Kong, Matthew R. Kroll, Brandon M. Lee, Paul F. Lee, Kevin M. Levine, Amy S. Li, Chengyu Liu, Max Mian Liu, Adam P. Lousararian, Peter B. Lowery, Allyson P. Mallya, Joseph E. Marcus, Patrick C. Ng, Hien P. Nguyen, Ruchik Patel, Hashini Precht, Suchita Rastogi, Jonathan M. Sarezky, Adam Schefkind, Michael B. Schultz, Delia Shen, Tara Skorupa, Nicholas C. Spies, Gabriel Stancu, Hiu Man Vivian Tsang, Alice L. Turski, Rohit Venkat, Leah E. Waldman, Kaidi Wang, Tracy Wang, Jeffrey W. Wei, Dennis Y. Wu, David D. Xiong, Jack Yu, Karen Zhou, Gerard P. McNeil, Robert W. Fernandez, Patrick Gomez Menzies, Tingting Gu, Jeremy Buhler, Elaine R. Mardis, and Sarah C.R. Elgin

Subjects
Drosophila, genome size, heterochromatin, retrotransposons, Wolbachia, Genetics, QH426-470
Abstract

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5′ ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

Published
2017
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2. Translational regulation of the DOUBLETIME/CKIδ/ε kinase by LARK contributes to circadian period modulation.

Author

Yanmei Huang, Gerard P McNeil, and F Rob Jackson

Subjects
Genetics, QH426-470
Abstract

The Drosophila homolog of Casein Kinase I δ/ε, DOUBLETIME (DBT), is required for Wnt, Hedgehog, Fat and Hippo signaling as well as circadian clock function. Extensive studies have established a critical role of DBT in circadian period determination. However, how DBT expression is regulated remains largely unexplored. In this study, we show that translation of dbt transcripts are directly regulated by a rhythmic RNA-binding protein (RBP) called LARK (known as RBM4 in mammals). LARK promotes translation of specific alternative dbt transcripts in clock cells, in particular the dbt-RC transcript. Translation of dbt-RC exhibits circadian changes under free-running conditions, indicative of clock regulation. Translation of a newly identified transcript, dbt-RE, is induced by light in a LARK-dependent manner and oscillates under light/dark conditions. Altered LARK abundance affects circadian period length, and this phenotype can be modified by different dbt alleles. Increased LARK delays nuclear degradation of the PERIOD (PER) clock protein at the beginning of subjective day, consistent with the known role of DBT in PER dynamics. Taken together, these data support the idea that LARK influences circadian period and perhaps responses of the clock to light via the regulated translation of DBT. Our study is the first to investigate translational control of the DBT kinase, revealing its regulation by LARK and a novel role of this RBP in Drosophila circadian period modulation.

Published
2014
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3. Facilitating Growth through Frustration: Using Genomics Research in a Course-Based Undergraduate Research Experience

Author

John M. Braverman, Kenneth Saville, Mollie K. Manier, Katherine C. Teeter, Sarah C. R. Elgin, Rachel Sterne-Marr, Debaditya Mukhopadhyay, Adam Haberman, M. Logan Johnson, Jacob D. Kagey, Emily Furbee, Matthew A. Escobar, Vida Mingo, Stephanie Schroeder, Srebrenka Robic, Anya Goodman, Catherine Reinke, Yuying Gosser, Meg M. Laakso, Mary A. Smith, Daron C. Barnard, Christopher Bazinet, Nathan T. Mortimer, Mary L. Preuss, Cindy Arrigo, Paul J. Overvoorde, Elizabeth Mitchell, Rebecca C. Burgess, Wilson Leung, Diane Sklensky, Laura K. Reed, Lindsey J. Long, Don W. Paetkau, Melissa Kleinschmit, Judith Leatherman, Olga R. Kopp, Janie Brennan, Joyce Stamm, Chunguang Du, Norma A. Velázquez-Ulloa, Thomas C. Giarla, Gerard P. McNeil, Justin Thackeray, Andrew M. Arsham, Jeremy Buhler, Jennifer A. Kennell, Sara J. Anderson, Leming Zhou, Takrima Sadikot, Alexis Nagengast, Susan Parrish, Heather L. Eisler, Dennis Revie, Leocadia V. Paliulis, Chiyedza Small, Anna K. Allen, Amy T. Hark, James E. J. Bedard, Lisa Kadlec, Jeffery S. Thompson, Paula Croonquist, James V. Price, Stephanie Toering Peters, Evan C. Merkhofer, Melanie Van Stry, Matthew Skerritt, Anne G. Rosenwald, Cindy Wolfe, Nicholas Pullen, Nighat P. Kokan, Sondra Dubowsky, Jamie Siders Sanford, Rebecca Spokony, Luis F. Matos, Christopher D. Shaffer, Consuelo J. Alvarez, Justin R. DiAngelo, Jennifer Roecklein-Canfield, Maria Soledad Santisteban, Sheryl T. Smith, Juan Carlos Martínez-Cruzado, Indrani Bose, Christopher J. Jones, Adam Kleinschmit, Brian Yowler, Karim A. Sharif, S. Catherine Silver Key, Amie J. McClellan, Matthew Wawersik, Jennifer C. Jemc, Carina E. Howell, Hemlata Mistry, Rivka L. Glaser, Shan Hays, Kimberly L. Keller, Michael R. Rubin, Martin G. Burg, David Lopatto, Charles R. Hauser, James J. Youngblom, Jennifer Leigh Myka, Michael S. Foulk, and Aparna Sreenivasan

Subjects
QH301-705.5, Process (engineering), media_common.quotation_subject, Frustration, General Biochemistry, Genetics and Molecular Biology, Education, Formative assessment, 03 medical and health sciences, Mathematics education, Biology (General), Set (psychology), lcsh:QH301-705.5, 030304 developmental biology, media_common, lcsh:LC8-6691, 0303 health sciences, LC8-6691, lcsh:Special aspects of education, General Immunology and Microbiology, Research, 4. Education, 05 social sciences, 050301 education, Special aspects of education, Focus group, lcsh:Biology (General), Undergraduate research, General partnership, Working through, General Agricultural and Biological Sciences, Psychology, 0503 education
Abstract

A hallmark of the research experience is encountering experimental difficulty and working through that challenge to reach success. The ability to overcome scientific challenges is essential to being a successful scientist, but replicating these challenges can be difficult in a teaching setting. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students’ learning experience in this research is continuous and recursive, frequently beginning with frustration but eventually leading to success. In order to explore our “formative frustration” hypothesis, we gathered data about this research experience from faculty via a survey, and from students both via a general survey and a small set of focus groups administered at the end of the GEP CURE. All three datasets contained comments mentioning frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of what we have deemed “formative frustration” is an important aspect for a successful CURE.

Published
2020
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4. Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element

Author

Rachael K Bridgman, Rachel A Greenstein, Maxine E Wykle, Insun Chong, Harrison Friedman, Casey Hanson, Kelly Drumm, Tingting Gu, Marium Feliciano-Camacho, Juliana Broussard, Jackie Alexander, Patrick A Schneider, Joyce Stamm, Kevin M. Levine, Jennifer Bland, Zenyth A Sheppard, Marlee B Nelson, Adam S Rinaldi, John M. Braverman, Elizabeth Zavala-Arellano, Nicholas C. Spies, Kara Tsukashima, Monika C Lemke, Ellen N Niemiec, Dale L. Beach, Krystal L Holtcamp, Mitchell J McDonald, Nadia Safa, Karim A. Sharif, Martin G. Burg, Diana L. E. Johnson, Danielle R Perry, Amy S Li, Victoria R Zellmer, Jack Y. Yu, Joan Q Lawrence, Nighat P. Kokan, Raquel Montañez-Gonzalez, Kaitlin E Homa, Perouza Parsamian, Kaitlyn E Takach, Shane M. Patao, Matthew Simon, Adam C Wernette, Chun L Ng, S Mariel Ramey, Gabrielle L. Hussey, Charles R. Hauser, Karolyn Barker, Danielle M Kramer, Alexis M Ceasrine, Mariela Taboas-Arroyo, Rebekah Lee, Alexandra L Hertz, Charlotte M Brown, Gabriel Stancu, Dorianmarie Vargas-Franco, Lindsey J Suriano, Kyle L. Jung, Sami Mamari, Gary R. Skuse, Thomas J Quisenberry, Laura K. Reed, Don W. Paetkau, Victoria Chevee, Kerry Campbell, Adam Haberman, Ghazal Stity, Antoinette E. Fafara-Thompson, Breanna Haiker, Maddison F McEvilly, Isaac C Veysey-White, Robert J Allen, Susana S Apiz-Saab, Madeline M Martin, Edward Himelblau, Laura T Vives, Arielle M Vasquez, Nathan T. Mortimer, Catherine O'Keeffe, Elizabeth J Villafuerte, Shannon R. McCartha, Kirsten Bickford, Max Kollmer, Henry Z Gong, Grzegorz L. Polak, Joanna J Smith, Terrance Embry, Katelynn E Deibel, Matt Van Camp, Devon E Schultz, Sarah Wai-Chee Kong, Leah E Waldman, Suzette M. Arias-Mejias, Yakov Shevin, Richard McGuire, Danny Mammo, Sarah K Hilton, Max Mian Liu, Jaclyn D Campbell, Robert W. Fernandez, Baljit Bedi, Jordan A Black, Christopher Scheiber, Chengyu Liu, Lindsay M Prescod, Lindsay M Corbeill, Patricia N Claudio-Vazquez, Jeremy Buhler, Michael J Pavia, Holly Lyn Robbins, Luis A. Jimenez, Tanveer Sandhu, James J. Youngblom, Jordan E. Matthews, Katherine Gavinski, Rahul Nadendla, Olivia A Pahl, Hien P Nguyen, Sasha Jia, Stephanie M Grieb, Joseph E Marcus, Michael B. Schultz, Amber M. Gygi, Emily A Morlock, Karina M Gonzalez-Bonilla, Paola Villegas, Jeffrey W Wei, Christopher J. Jones, Guadalupe Quintana, Kaidi Wang, Hiu Man Vivian Tsang, Ruchik Patel, Heaven L Cerritos, Thomas C. Giarla, Gerard P. McNeil, Michael R. Rubin, Mary E Franks, Jordan R Ramirez, Maiye Her, Matt Segal, Mark Scheuerman, Emmy E. Ogawa, Darryl Lopez, Robert M. Gingras, Simon Hsu, Amy T. Hark, Zuzana Kocsisova, Dennis Revie, Christopher Bazinet, Kevin Ko, Jeremy S Davis, Deana Gabbard, Amanda Boozalis, Suchita Rastogi, Jeffery Bettincourt, Laura Schiraldi, Edward A Horansky, Amanda H Cox, Susan Parrish, Kristine Ostby, Sarah M. Jacobs, Jesse J Ensign, Kevin Kumimoto, Paul F Lee, Nicholas U. Schwartz, David D. Xiong, Susan E Herman, Allison E. McClish, Averill D Guo, Cody M Mittig, Heran Gebreyesus, Allison R Wagner, Katherine J Olson, Lucy Huo, William D. Barshop, Victoria R Sochor, Francisco J Rivera-Rosario, Samatha K Begley, James E. B. Docherty, Brandon Lee, Eric P. Spana, Abubakarr Bangura, Sarah A Einsteen, Luke Schmidt, Arianne E. Rodriguez, Samantha Parsons, Ryan Duggal, Karen Zhou, George Odisho, Tam Vuong, Erin Duso, Adam P Lousararian, Stephanie L Christ, Christopher D. Shaffer, Myrielis Rivera-Burgos, Sam Asinof, Dennis Y. Wu, Torie L Richardson, Heather L. Eisler, Allyson P Mallya, Brittney Stanton, Elizabeth J. Chen, Laurie Cannon, Briana D McRae, Peter B Lowery, Alicia R Carroll, Judith Leatherman, Guillermo Perez-Aragon, Joshua M Lorenz-Guertin, Delia Shen, Erica Enoch, Peter Wendland, Wilson Leung, Elaine R. Mardis, Adam Schefkind, Thomas Q. Xu, Wint Yan Aung, Darrin T. Schultz, Misha A Host, Hani Yosif, Ashleigh P O'Reilly, Eric Spencer, Melissa D. Patao, Jonathan M Sarezky, Matthew R Kroll, Casey L Personius, Alice Turski, Julie Beth Gillespie, S. Catherine Silver Key, Hashini Precht, Harriette Carrington, Stella Rosen, Yi Huang, Joseph Perez-Otero, Jeanette Hauke, Elizabeth A S Rettie, Petros Svoronos, Nicholaus Monsma, Kelsey F. Sugrue, Latia Britt, Tracy Wang, Patrick Gomez Menzies, Alycia Zoellner, Francesca M Gifford, Carlos F Carrion-Ortiz, Lyndsay D Kirkland, Ryan Moran, Vinayak S. Nikam, Spencer M Batten, Vanessa P Chu, Justin R. DiAngelo, Sheryl T. Smith, Ximena Velez, Tara Skorupa, Alen Ramic, Ricky Prasad, Richard Forka, Ken Saville, Ben Chlebina, Robert Franklin, Drew Miller-Foreman, Judith A Ingles, Rohit Venkat, Jennifer J Palomino, Debbie M Espada-Green, Cassie M Modahl, William A Hilton, Tracy Selfridge, Mona O Rodriguez, Samantha House, Srebrenka Robic, Sarah C. R. Elgin, Patrick Ng, Masud Karimi, and Zachariah Wichman

Subjects
0301 basic medicine, Genetics, Euchromatin, biology, Drosophila ananassae, heterochromatin, Retrotransposon, Investigations, QH426-470, biology.organism_classification, Genome, retrotransposons, 03 medical and health sciences, 030104 developmental biology, Codon usage bias, genome size, Drosophila, Drosophila melanogaster, Molecular Biology, Genome size, Gene, Genetics (clinical), Wolbachia
Abstract

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5′ ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

Published
2017
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5. Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

Author

Raechel Harnoto, Morgan C. Anderson, Amy Z. Xu, Heather Hedeen, Arnaldo J. Santiago-Sanabria, Brandy L. Hammond, Kenneth Saville, Ross D. Kooienga, Christopher Chesley, Robert W. Morris, Aubree T. Gillis, Brittney Offenbacker, Katherine C. Palozola, Trisha Tomkins, Nicole Yu, Matthew Kwong, Megan E. Aldrup, Jordan E. Kus, Chelsey Friedrichs, Kenneth Stapleton, Carly E. Pelchen, Norma Chamma, Joshua F. Machone, Danielle Kulich, Andre Kennedy, Matt J. Crowley, Daniel Broomfield, Adeola Adebayo, Nicolas Ragland, Shady Messiah, Jonathan Misch, Meghan B. Rooney, Eva N. Rubio-Marrero, Will Sherrill, Joyce Stamm, Rachel R. Leads, Lindsey Shantzer, Alexis J. Scott, Andrew W. Waggoner, Kristen M. Cooper, Adam Haberman, Carmen A. Watchinski, Marcos A. Perez, Lisa Kadlec, Kiara N. Medina-Ortega, Kayla Chapman, Cheryl Bailey, Nicholas Fazzio, Insun Chong, Lasse Schmidt, Darla M. Balthaser, Megan DeShetler, Jien Shim, Anna Rogers, Chris Uitvlugt, Bryan Yarrington, Ruth A. Howe, Andrea Ochoa, Gregory J. Mullen, Young Lu Kim, Olivia L Knowles, Kevin M. Levine, Matthew M. Villerot, Thomas J. Rose, Jonathan E. Smith, Sukhjit Kaur, Roshni Patel, Olivia Plante, Tenzin Choeying, Jennifer R. Ramthun, Tiffany Y. Y. Choi, Michael Rahimi, Guzal Khayrullina, Lauren R. Boudreaux, James E. J. Bedard, Brian A. Dow, Christopher A. Louie, Kenneth S. Smith, Joannee Zumkehr, Marcus Gostelow, Melissa A. Tache, Tiffany Dai, Joan D. Zambrana-Burgos, Lauren R. Meyer, Carter Brown, Adam Brown, Travis Lamb, Carissa Belella, Hannah Gilman, David DuPuis, Ramón E. Rivera-Vicéns, Priyanka Naik, Anna L. Shipman, Jad El-Adaimi, Eric Spencer, Jonathan D. Marra, Melissa D. Patao, Sharon Ibarra, Jiayu Zhang, Ashley Vetor, Bobbi Botsford, Jenifer Winters, Nelson A. Valentín-Feliciano, Lauren M. Robinson, Christopher R. Macchi, Jennifer Hernández-Muñiz, E. Gloria C. Regisford, Jaelyn L. Johnson, Cory M. Dauphin, Tezin A. Walji, Matthew A. Zaborowicz, Stacey Winkler, Shannon M. Lowell, Marly R. McCracken, Andrew Adams, Lindsay A. Spaeder, Matthew W. Wolski, Adrese Kandahari, Fabiola Robles-Juarbe, Bryce A. Turner, Ángel L. Laboy-Corales, David T. Watson, Elaine J. Durchholz, Vanessa Rodriguez, Emily J. Teepe, Alaina C. Conturso, Eric Nyabeta Onsarigo, Tijana Martinov, Rohit Venkat, Charles R. Hauser, Priya Srikanth, Marwan Ibrahem, Karl E. Smith, Jessica M. Tucci, Ethan J. Brock, Aparna Sreenivasan, Jasmine Hales, Brianna K. Barnard, Andrew P. Stein, Jessica G. Thomas, Mallory Perella, Lorraine Rodriguez-Bonilla, Shekerah Primus, Zachary D. Moore, Caitlin M. Ament, Amber N. Hare, Brad Pamnani, Eugenia A. Soliterman, Christina Paluskievicz, Yashira M. Valentín-Feliciano, Alexandra K. Eckardt, Anya Goodman, Joseph W. Noynaert, Ashlee G. Johnson, Tyneshia C. P. Henry, Camille D. Ratliff, Ian O. Chase, Michel A. Conn, Jessica Koehler, Daniela Martiniuc, Allison J. Schepers, Megan B. Vylonis, Chrystel Dol, William Dirkes, Michelle S. Rivera-Llovet, Susana Rodríguez-Santiago, Heather L. Eisler, Mary L. Preuss, Daymon Peterson, Martin G. Burg, Aaditya Khatri, John R. Woytanowski, Holly Schiedermayer, Dara Cohn, Leah E Waldman, William M. Morris, Sharon C. Ehret, Marianna Defendini-Ávila, Jessica Fese, Suzette M. Arias-Mejias, Anna Kammrath, William D. Barshop, Edwin G. Ramírez-Aponte, Luis A. Jimenez, Carolina Marques dos Santos Vieira, Cody D. Kern, Francheska M. Delgado-Peraza, Tiffany Wan, Janice L. Krumm, Osagie Ighile, Eric D. Sassu, Jess M. Darusz, Laura Rodela, Daniel S. Nicolas, Shubha Govind, Mary Miller, Joseph E Marcus, Jason Pollack, Rostislav Castillo, Daniel Coomes, Matthew J. Borr, Diana Pérez-Afanador, Lucas A. Watson, Hannah C. Koaches, Amber Quintana, Faith H. Kung, Cameron B. Harris, Bridget M. Janssen, Cristina Zambrana-Echevarría, Jennifer K. Jones, Ian Dobbe, Benjamin M. Lewis, Lena N. Lupey, Julia A. Hilbrands, Cristina Montero Diez, Jorge L. Santiago-Ortiz, Dustin S. Woyski, Sandy D. Mach, Joseph Perez-Otero, Karim A. Sharif, Carlos Mendoza, John D. Fitzgibbons, Nelson H. Knudsen, Christy MacKinnon, Hayley M. Faber, Kwabea Agbley, Michelle Heslop, Olivia Cyrankowski, Priscilla Rodriguez, Melissa Jones, Jean M. Strelitz, Ryan A. Grove, Rachel A Greenstein, Michael Murillo, Elizabeth Greiner-Sosanko, Ciani Jean Sparks, Darryl McFarland, Franca G. Rossi, Heran Gebreyesus, Chris Kay, Danielle Ladzekpo, Chris Harward, Jordan S. Christie, Consuelo J. Alvarez, Elaine V. Morlock, Geoff Scott, Kelsey Hockenberger, Sepo Musokotwane, Adam Fearnow, Lauren J. Keny, Alaina J. Grantham, Evangelina Reza, Mike Colgan, Melanie K. Regan, Stephanie J. Potocny, Sasha L. Dorsett, Tara Skorupa, Valerie M. Gónzalez-Pérez, Vinayak S. Nikam, Anne C. Meier, Varun Sundaram, Helen B. Rankin, Andrew B. Nylander, Mariela Gines-Rosario, Laurell MacMillian, Jeannette M. Osterloh, Robert H. Allen, Melanie A. Smith, Sarah J. Spencer, Cheri M. Ackerman, Jeffrey L. Poet, Amanda J. Hay, Isaac O. Armistead, Laura K. Reed, Don W. Paetkau, Bib Yang, Enid M. Quintana-Torres, Kathryn L. Golden, Lauren A. DiLorenzo, Alen Ramic, Mark T. LeBlanc, Carl J. Minniti, Robert J. Bailey, Kristen M. Thomsen, Ashley L. Adams, Chad A. Koplinsky, Eliezer O. Perez-Colomba, Nicole A. Howey, Katie A. TerMeer, Stephanie Intriago, Christina N. Kufel, Mary Waters, Bo Liu, Thomas J. Bahr, Ashley R. Miller, Claire Pattison, Morgan R. Light, Amy T. Hark, Jennifer S. Doty, Catherine M. Mageeney, Adam J. Ronk, Nadezhda Fefelova, Andrew R. Armstrong, Maida Chen, Elizabeth Macias, Kim M. Chau, Paul Bilinski, Trevor G. Floyd, Cassidy T. Lee, Jenna C. Tenney, Bob Gardner, Patricia Ortiz-Ortiz, Elizabeth S. Jewell, Gabi Lucas, Brandon Lee, Jenifer N. Jarrell, Jimmy Hsiang-Chun Chang, Lorraine Malkowitz, Ulises Marrero-Llerena, Gabriel Stancu, Matthew R. Unzicker, Andrea P. Burgos-Bula, Michelle L. Miller, Elisandra Rivera, Kate Bagaeva, Jessica W. Polk, Jordan E. Carney, Maureen Corrielus, Jana Nietmann, Jeff Howenstein, Elizabeth Kiernan, Sabya A. Rauf, Brandon M. Katz, Elizabeth C. Nordman, Devon Shallman, Eric M. Clark, Lenin Lopez, Karen J. Kraftmann, Leslie Guadron, Julia Kuhn, Allison R. Schneiter, Satish C. Bhalla, Emily J. Howell, Blair Undem, Jeffrey S. Thompson, Arelys Flores-Vazquez, John Kiley, Cody M. Morrow, Joseline Serrano-González, John Mark Knepper, Christopher Beck, Calise Debow, Anna L. Smith, Angelica Garcia, Shelbi Christgen, Shadie Emiah, Tammy Mazur, Rachel E. VanDyken, Frank R. Soto delValle, Zachary Nichols, William R. Kennedy, Ameer Zidan, Douglas A. Herrick, Thomas Q. Xu, Elizabeth Shoop, Jessica A. Kampmeier, John M. Kerber, Caitlin Pozmanter, Emily L. Hong, Frederic J. Deuschle, Allyson B. Rivard, William Neutzling, Joseph V. Moran, Benjamin K. Johnson, Jacob Jipp, Shannon R. McCartha, Abby Vrable, Z. Goodwin, Suchita Rastogi, Alyssa M. Newman, Lionel Ortiz-Fuentes, Arjun A. Anilkumar, Bryan M. Hennessy, Hui-Min Chung, Katie L. Goeller, Carlos E. Santos-Ramos, Adam Dillman, Christine D. Wilson, Sarah J. Peacock, Andrew J. Kim, Carol I. Morales-Caraballo, Briana Brinkley, Justin Alldredge, Rebecca Krock, Kristen C. Davis, David Dunbar, Joshua L. Manghelli, Erica K. Earl, Katherine Gavinski, Sheryl T. Smith, Portia Mason, Lindsay J. Hoogenboom, Jessen T. Havill, Sonya G. Méndez-Castellanos, Darrin T. Schultz, Katherine J. Faber, Allison O’Rouke, Emily G. Miller, Yara Ashrawi, Curtiss E. Lane, Saryleine Ortiz-DeChoudens, Michael W. Sandusky, Andrew Montgomery, Rita Kabaso, Todd Aronhalt, Jonathan D. Foust, Jorge Ruiz, Eric Helmreich, Todd T. Eckdahl, Charlotte Lea, Kevin Coulson, Kristin M. French, Kate A. Woodard, Brandon J. Burkhart, Kylie McNeil, Curtis R. Edwards, Jimmy Ma, Darcie D. Elder, Tia DiTommaso, Nicholaus Monsma, Sarah A. Jelgerhuis, Stephanie J. Adams, Nichole Rigby, Heather L. Holderness, Charlotte Williams, Megan Donegan, Taylor S. Harding, Javier O. Martinez-Rodriguez, Sandeep Venkataram, Tiffany Wong, Anika Toorie, Jenny L. Rose, Ashley S. Brown, Sarah A. Popelka, Matthew Williams, Julie Bryant, Sarah C. R. Elgin, Sonali Kumar, Joshua Burkhardt, William J. Puetz, Erica L. Alvendia, Richard A. Tumminello, Kesley Parry, Joshua R. Smith, Ashley F. Custer, Carlos E. Ortiz, Yedda Li, April E. Bednarski, Simon Ng, Max Mandelbaum, Arlene J. Hoogewerf, Chelsea A. Walker, Ryan S. Lee, Jeannette Wong, Isabella Theresa Felzer-Kim, Harrison Friedman, Megan Bourland, Luis R. Colón-Cruz, Lucy Liu, Nicole C. Olson, Yi Ren, Adam P Lousararian, José M. Cruz-García, Charlie Manchee, Kyle Zoll, Kristina M. Stemler, Juliana Belén-Rodríguez, Ashley S. Timko, Jane Lopilato, England Raimey, Amy D. Melton, Joshua D. Forsyth, Christopher D. Savell, Himabindu Reddy, Alica B. Allen, Amanda Maffa, Daniel W. Cassidy, Luciann Bracero-Quiñones, Eric Lemmon, Justina R. Bartling, Bradley J. Ogden, Petros Svoronos, Mary Spratt, Lisa Sudmeier, Héctor A. Martell-Martínez, James F. Geary, Bridget J. Sessions, Christopher Campana, Kaitlyn A. Downey, Seth G. Dawson, Daniella Menillo, Casey Hanson, James M. Bellush, Justin A. Gonzales, Roy Song, Karvyn Torchon, Betsy Hoover, Michael Closser, Lacey Neufeld, Micah Shelton, Benjamin R. Does, Juan Carlos Martínez-Cruzado, Jordan S. Baumgardner, Nicole Chichearo, Mary T. Reilly, Colleen V. Kelley, Monica Yalamanchili, Dawn Lau, Abbie Morgan, Alyssa Cifelli, Milton R. Herrold, Ambreen Khan, James Messler, Kyle Westphal, James L. Kehoe, Juliana A. Wurzler, Garrett Salzman, Tracy Wang, Charlene Emerson, Lyndsey A. Reynolds, Alysha Moretti, Marita K. Abrams, Mara G. Cole, Michael B. Schultz, Samantha Cruz, Natalie Ngai, Nadia Safa, Vicente Velasquez, Ashley Townsend, Jonathan L. Crooke-Rosado, Amber M. Gygi, Ishwar S. Gill, Christopher McLaughlin, Dorianmarie Vargas-Franco, Alissa Beckett, Samantha Vue, Nadine L. Rossi, Justina Chinwong, Ryan Michael Rempe, Trip Freeburg, Amy J. Johnson, Omolara Glenn, Jade Lea Rekai, Hashini Gunasinghe, Vivienne Echendu, Marshall Strother, Morgan Baker, Christopher D. Smith, Paolo A. DaSilva, Noelle Delacruz, Tiara Tirasawasdichai, Yakov Shevin, Wilfried Guiblet, Shane M. Patao, Peterson R. Cullimore, Giancarlo F. Garbagnati, Adam E. Musick, Sarah C. Butzler, Jonathan D. Presley, Ana I. Correa-Muller, Christopher D. Shaffer, Chunguang Du, Ryan D. Mitchell, Jonathan P. Rennhack, Barbara L. Hopkins, Mary E. Shaw, Jessica E. Hill, Jeremy N. Wong, Anna Kim, Christopher B. Khoury, Julia Chapman, Amanda T. Mercer, Jessica A. Shuen, Joyce H. Lau, I.N. Falk, Sunil Rathore, Christopher J. Jones, Laura Simone Bisogno, Nighat P. Kokan, Paul Yenerall, Amber L. Price, Kelsey T. Bushhouse, Stephen L. McDaniel, Andrew P. Drake, Johnathan D. English, Sampson K. Boham, Robert A. Herbstsomer, Daniel S. Fosselman, Kevin Babilonia-Figueroa, Matthew Simon, Anne G. Rosenwald, Bryan J. Rupley, Heather Cohen, Victoria Scala, Avery B. Cromwell, Christopher E. Blunden, Yelena P. Davis, William B. Armstrong, Kristine Ostby, Joanna Haye, Lauren M. Wysocki, Lena Christiansen, Allison A. Throm, Sarah Flohr, Matthew Wawersik, Rebecca J. Cotteleer, Kristen R Ramirez, Dontae A. Jacobs, Sarah Woehlke, Gregory S. Messenger, Soham Aso, Nicole Clarke-Medley, Bryant R. Swanson, Lindsay K. Brouwer, S. Catherine Silver Key, Stephanie Zarrasola, Michael S. Salgado, Dong K. Rhee, Mai Abdelnabi, Eve VanEck, Jeremy Buhler, Sarah Kong, Turner Conrad, Jennifer Roecklein-Canfield, Marykathryn Tynon, Brian J. Maniaci, Alexa M. McDonough, Ivan G. Llavona-Cartagena, J. Devin Spencer, Todd D. Johnson, Azita Bashiri, Kimberley Ramsey, Mike Polen, Hien P Nguyen, Seantay D. Patterson, Lucia Wande, Nicholas U. Schwartz, Han Yuan, Albeliz Santiago-Colón, Joseph Medina, Samuel Thomas Crowley, Emma Shoemaker, Alex J. Feliciano-Cancela, Alexander J. Kujawski, Lillyann Asencio-Zayas, Gentry L. Pickett, Matt J. Randazzo, Erica Stagaard, Kristin M. LaForge, Gabriela A. Llaurador-Caraballo, Anastasia K. Yemelyanova, Alan Tseng, Erika E. Menyes, Julie Azarewicz, Christa Burke, Samuel I. Smith, Nazanin Ghavam, Carolina Gomez, Cameron Fick, Anthony Pinto, Lindsay Rios, Gary A Kuleck, Ashley Rich, Kayla A. Florian, Martin N. Cheramie, Yuki Kwan Wa Shum, Atlee Baker, LaJerald Augustine, Alyson Greenwell, Rasleen K. Saluja, Jason S. Macias, Wesley W. Winn, Samantha M. Schmuecker, Michelle E. M. Eisen, Pedro Benitez, Jeanette Hauke, Nora C. Goscinski, Justin R. DiAngelo, Carter T. Docking, David D. Xiong, Brittany D. Pasierb, Matt Van Camp, Yin Zheng, Nikie L. McCabe, Emily Reed, Katie Homa, Kimberly S. Kolibas, Elizabeth A. Karaska, Grace A. Dougherty, John P. Fanning, Michael Fasano, Joseph E. Sable, Robert W. Schulz, San Francisco Nguyen, Michael L. Rojas-Vargas, Kierstin L. Naylor, Emily Peoples, Jessica Neely, Lejla Cesko, Brionna D. Davis-Reyes, Roxanne Banker, Amanda K. Tilot, Jordan P. Brand, William H. Newhart, Lauriaun Johnson, Michelle M. Giddens, Nicole B. Clark, Anant Agarwalla, Thomas F. Minton, Dana W. Brooks, Amanda D. Garrett, Bethany M. Klett, Kristin M. Starkey, Antoinette E. Fafara-Thompson, Michael R. Rubin, Jonathon M. Benson, Erica Enoch, Amanda M. Damsteegt, Zackary W. Scott, Elisabeth A. Kelly, Jason M. Barnett, Wilson Leung, Luke J. Rodriguez-Giron, Krishna C. Mudumbi, Francis J. May, Nadyan M. Vargas-Barreto, Geeta Statton, José L. Torres-Castillo, Sarah Hirsch, Rachel M. Reem, Linghui Li, Deirdre Robinett, Jason Caronna, Abneris E. Rodríguez-Laboy, Samantha Lawrence, Katherine R. Reynolds, Corinne Weeks, Allison M. Sterling, Chun Leung Ng, Roman E. Ramirez, Daron C. Barnard, Leming Zhou, Eric P. Spana, John A. Toth, Alvin Lu, Krizia C. Menéndez-Serrano, Jonathan M. Heckman, Ben Chlebina, Matthew C. Fadus, Helmet T. Karim, Shailly Gaur, Timothy R. Jelsema, Nicholas Keysock, Thomas J. Carr, Zach Fusco, Evan M. Verbofsky, Monal Naik, Amanda H. Flores, Kristin A. Knouse, Olga R. Kopp, Elizabeth Feenstra, Edward P. Sweeney, Christen Johnson, Justin Crawford, Damian Urick, Victor W. Mullen, Carrie A. Dunham, Gabriella A. DeMichele, Mengyang Sun, William Harrington, Jessica M. Bodenberg, Xavier A. Collado-Méndez, T. Aaron Wiles, Michelle K. Powers, Phillip J. Minnick, Lourdes N. Irizarry-González, Valeria Silva, Steven Ovu, Nik Kolba, Peter Lindbeck, Jerome M. Molleston, Ifeanyi Obiorah, David Carranza, Lauren R. Beck, Alina M. Tamayo-Figueroa, Elaine R. Mardis, Rachel N. Lippert, Ingrid T. Rivera-Pagán, Mahdi Soos, Trung T. Nguyen, Megan Martinez, Van Kim, Benjamin L. Danner, Randall J. DeJong, Melissa M. Trieu, Andrea M. Senquiz-Gonzalez, Mary Grace Schueler, Emily E. Magnuson, Lesley E. Jackson, Hendrick Pagán-Torres, Fareed Sanusi, Dana Koenig, Vidya Chandrasekaran, Chinmoy I. Bhatiya, Dongyeon Kim, Paul J. Overvoorde, Reece Watson, Jennifer Schottler, Devry Lin, Jim Youngblom, Taylor Schauder, Nigel Madden, Isabel Valdez, Thomas John Reynolds, Kelly M. Deranek, Anne A. Welker, Jackie X. White, Nicole C. Riddle, Jacob Pfeil, Aldo Heredia-Negrón, Christine Langner, Tao Jian He, Jonathan P. Mecoli, Lissett Mayorga, Scott Chiang, Rishi Singhal, Julia C. Peairs, Michael Quach, Anne M. Eime, GiNell Elliott, Meleah J. Gross, Melissa Drewry, Julia A. Emerson, Anthony K. Lambright, Isaac Appiah, Gregory M. Robertson, Nathaniel Regenold, Philip Pham, George Odisho, Alexi Archambault, Matthew Dothager, Shana M. Baldassari, Paul J. Lee, Callie R. Merry, Jesse R. Farek, Archana Tare, Srebrenka Robic, William Vernon, Tam Vuong, Bethany Grace Bonifield, Katrina Thistle, Rose M. Dowd, Noor Tazudeen, Jennifer Weaver, Manpreet Kaur, Nicole M. Caesar, Yi Zhang, Michael C. Cristostomo, Albert Tzeng, Kayla Vondy, Emily Perling, Ramiro A. Chavez, Lanor S. Horton, Matt Kroll, Levent H. Beken, Justin R. Starcher, Sam Asinof, Nathalia M. Cruz, Eunice George, Adam T. Morrow, Heather Milnthorp, Cheryl Mazzeo, Kristen R. Hatfield, Anna L. Boudoures, Ashley A. Tewilliager, Edna P. Tascón-Peñaranda, Vilma F. Huerta, Sarah Tuberty, Mallory A. Williams, Rachel E. Weber, Sarah Spencer, Emily C. Leatherman, Yuying Gosser, Steve DeFazio, Patrick Ng, Jeri Sparks, Pavan Bhat, Mindy E. Bower, Jordan E. Matthews, Cyrus E. Kuschner, Anne Bertolet, Matt Kusner, Thomas C. Giarla, Jessica Penn, Gerard P. McNeil, Mariam Meghdari, Michael J. Wolyniak, Matthew Juergens, Karla I. Velázquez-Soto, Maria Kaisler, Jeanine Schibler, Alexis Nagengast, Susan Parrish, Frances Marín-Maldonado, Shiv Mohini, Jessica King, Danny Mammo, Katherine S. Harker, Allyson P. Hawkins, Kelly Drumm, Jennifer A. Lammers, Allyson P Mallya, Ashley Bryant, Katie Weihbrecht, Pete Wendland, Gabriela V. Bernal-Vega, Nestor A. Gutierrez, Armando G. Bermudez-Capo, Luke R. Salbert, Kirk Haltaufderhyde, Michelle L. Kappes, Mary A. Smith, York Chen, Miguel Vélez-Vázquez, Brittany E. Plescher, Francis D. Beauchamp-Pérez, Alyssa Ward, Andrea N. Clary, Don Foret, Mitchell J McDonald, Mariela Colon-Vazquez, Amanda L. Blaker, Hao Yang, James Z. Liu, Austin B. Limle, Henry Huang, Luis Vilanova-Velez, Edgar Garibay, Philip J. Freda, Laura L. Mays Hoopes, Maureen S. Hammond, Marian M. Kaehler, Rebecca Shuford, Ray Sunjed, Cynthia K. Hanson, Marielle VanderVennen, Idaliz M. Martínez-Traverso, Jack Y. Yu, Spencer L. Franchi, Michael Snavely, John E. Anderson, Lainey S. Rubin, Kelly K. Jones, Stephanie F. Mel, Stacey Lytle, Danny L. Tran, Chelsea R. Barberi, Max Mian Liu, Eric A. Nollet, Sarah E. Muller, Diana Norton, John M. Braverman, Thu A. Phan, Nelson Membreno, Colin Khoshabian, John Gooch, Cassandra Kubricky, Priscila M. Rodríguez-García, Anna Wylie, Diana L. E. Johnson, Anna K. Unruh, Deborah Hammett, Jon Sarezky, Marie Brown, Carolina Riascos-Cuero, Emily J. Diekema, Emmy E. Ogawa, Miranda Chavez, Zuzana Kocsisova, Dennis Revie, Anniken M. Lydon, Peter A. Cognetti, Ashley A. Collins, Tariq Abusheikh, Erin K. Luippold, Kevin Myirski, Brian O. Rodríguez-Echevarría, Haley J. Plasman, Lara Baatenburg, Jesse Hendriksma, Christopher R. Knob, Max Semon, Cassandra Farrar, Xiao Zhu, Ali Dobbe, Marie-Isabelle B. Seydoux, Griffin Sadovsky, Shreya Prasad, Victoria Newcomb, Chad Gier, Dmitri Serjanov, Jules Wellinghoff, Maxwell T. Smith-Gee, and Alexandra H. Scoma

Subjects
Transposable element, Codon Adaptation Index, Euchromatin, Heterochromatin, transposons, evolution of heterochromatin, Investigations, Genome, Evolution, Molecular, 03 medical and health sciences, gene size, 0302 clinical medicine, melting characteristics, Species Specificity, codon bias, Genetics, Animals, Drosophila Proteins, Selection, Genetic, Codon, Molecular Biology, Genetics (clinical), 030304 developmental biology, Polytene Chromosomes, Repetitive Sequences, Nucleic Acid, Gene Rearrangement, 0303 health sciences, biology, Computational Biology, Molecular Sequence Annotation, Gene rearrangement, Exons, Genomics, biology.organism_classification, Introns, Drosophila melanogaster, Codon usage bias, DNA Transposable Elements, Drosophila, 030217 neurology & neurosurgery
Abstract

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.

Published
2015

6. A Course-Based Research Experience: How Benefits Change with Increased Investment in Instructional Time

Author

Juan Carlos Martínez-Cruzado, Gary A Kuleck, Shubha Govind, Christopher D. Smith, Judith Leatherman, Jeffrey S. Thompson, Daron C. Barnard, Christopher J. Jones, Paul J. Overvoorde, Matthew Wawersik, Amy Frary, Randall J. DeJong, Dale L. Beach, Todd T. Eckdahl, Laura L. Mays Hoopes, Marian M. Kaehler, David Lopatto, Justin R. DiAngelo, Michael R. Rubin, Mary A. Smith, Carina E. Howell, Donald R. Frohlich, Chunguang Du, Leming Zhou, Eric P. Spana, Stephanie F. Mel, John M. Braverman, Karim A. Sharif, Consuelo J. Alvarez, Gary R. Skuse, Cheryl Bailey, Anya Goodman, Kari Clase, Laura K. Reed, Anne G. Rosenwald, Don W. Paetkau, James E. J. Bedard, Mary L. Preuss, Gerard P. McNeil, Michael J. Wolyniak, Martin G. Burg, Lisa Kadlec, Alexis Nagengast, Susan Parrish, Hemlata Mistry, Hui-Min Chung, Joyce Stamm, April E. Bednarski, Sheryl T. Smith, Aparna Sreenivasan, Paul Szauter, Celeste Peterson, Stephanie Schroeder, Nighat P. Kokan, Satish C. Bhalla, Arlene J. Hoogewerf, Heather L. Eisler, Christy MacKinnon, Mary Spratt, Christopher Bazinet, Amy T. Hark, Wilson Leung, Olga R. Kopp, Diana S Johnson, Elaine R. Mardis, Mary E. Shaw, Catherine Reinke, David Dunbar, Yuying Gosser, Jane Lopilato, Vidya Chandrasekaran, Srebrenka Robic, Sarah C. R. Elgin, Kenneth Saville, Adam Haberman, Dennis Revie, Christopher D. Shaffer, Jennifer Roecklein-Canfield, Julia A. Emerson, Adam Kleinschmit, Jeremy Buhler, Charles R. Hauser, James J. Youngblom, S. Catherine Silver Key, and O'Dowd, Diane K

Subjects
Value (ethics), Program evaluation, Time Factors, General Biochemistry, Genetics and Molecular Biology, Information science, Education, Surveys and Questionnaires, Mathematics education, ComputingMilieux_COMPUTERSANDEDUCATION, Humans, Learning, Cooperative Behavior, Curriculum, Biology, Mathematics, Data collection, Genome, Data Collection, Research, Molecular Sequence Annotation, Articles, Genomics, Investment (macroeconomics), Faculty, Research Personnel, Variety (cybernetics), Knowledge, Undergraduate research, Attitude, Self Report, Curriculum and Pedagogy, Program Evaluation
Abstract

While course-based research in genomics can generate both knowledge gains and a greater appreciation for how science is done, a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. Nonetheless, this is a very cost-effective way to reach larger numbers of students., There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. An alumni survey revealed that time spent on a research project is also a significant factor in the value former students assign to the experience one or more years later. We conclude: 1) implementation of a bioinformatics project within the biology curriculum provides a mechanism for successfully engaging large numbers of students in undergraduate research; 2) benefits to students are achievable at a wide variety of academic institutions; and 3) successful implementation of course-based research experiences requires significant investment of instructional time for students to gain full benefit.

Published
2014
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7. The Genomics Education Partnership: Successful Integration of Research into Laboratory Classes at a Diverse Group of Undergraduate Institutions

Author

E. Gloria C. Regisford, Jeremy Buhler, Christopher D. Smith, Cheryl Bailey, Laura L. Mays Hoopes, Marian M. Kaehler, Anne G. Rosenwald, Elizabeth Shoop, Satish C. Bhalla, Yuying Gosser, Mary Shaw, Donald R. Frohlich, Gary A Kuleck, Gerard P. McNeil, Barbara A. Wilson, Joyce Stamm, Daron C. Barnard, Alexis Nagengast, Susan Parrish, Stephanie Schroeder, Jeffrey S. Thompson, Jennifer Leigh Myka, Consuelo J. Alvarez, Chitra Chandrasekaran, Christopher D. Shaffer, Robert W. Morris, Jim Youngblom, Paul J. Overvoorde, Mary Spratt, Diana L. E. Johnson, Todd T. Eckdahl, Charles R. Hauser, Vidya Chandrasekaran, Christopher J. Jones, David Lopatto, Kelynne E. Reed, Mary A. Smith, Robert Moss, Gary R. Skuse, Anya Goodman, Sarah C. R. Elgin, Wilson Leung, Olga R. Kopp, Nighat P. Kokan, Chunguang Du, Jeff L Poet, Elaine R. Mardis, Dennis Revie, Matthew Wawersik, Ken Saville, Douglas R Dorer, Hui-Min Chung, and Eric P. Spana

Subjects
Genetic Research, Universities, Genomics, Science education, General Biochemistry, Genetics and Molecular Biology, Education, 03 medical and health sciences, Annotation, Pedagogy, ComputingMilieux_COMPUTERSANDEDUCATION, Animals, Students, Curriculum, 030304 developmental biology, 0303 health sciences, Medical education, 4. Education, 05 social sciences, Educational technology, 050301 education, Articles, Faculty, ComputingMethodologies_PATTERNRECOGNITION, Undergraduate research, General partnership, Active learning, Laboratories, 0503 education
Abstract

Genomics is not only essential for students to understand biology but also provides unprecedented opportunities for undergraduate research. The goal of the Genomics Education Partnership (GEP), a collaboration between a growing number of colleges and universities around the country and the Department of Biology and Genome Center of Washington University in St. Louis, is to provide such research opportunities. Using a versatile curriculum that has been adapted to many different class settings, GEP undergraduates undertake projects to bring draft-quality genomic sequence up to high quality and/or participate in the annotation of these sequences. GEP undergraduates have improved more than 2 million bases of draft genomic sequence from several species of Drosophila and have produced hundreds of gene models using evidence-based manual annotation. Students appreciate their ability to make a contribution to ongoing research, and report increased independence and a more active learning approach after participation in GEP projects. They show knowledge gains on pre- and postcourse quizzes about genes and genomes and in bioinformatic analysis. Participating faculty also report professional gains, increased access to genomics-related technology, and an overall positive experience. We have found that using a genomics research project as the core of a laboratory course is rewarding for both faculty and students.

Published
2010

8. The Drosophila RNA-binding protein Lark is required for localization of Dmoesin to the oocyte cortex during oogenesis

Author

Manpreet Kaur, Gerard P. McNeil, Ruth Kang, and Sheryl Purrier

Subjects
Genetics, Membrane Proteins, RNA-Binding Proteins, RNA, RNA-binding protein, Biology, Actin cytoskeleton, Oocyte, Oogenesis, Cell biology, medicine.anatomical_structure, RNA splicing, Oocytes, medicine, Animals, Drosophila Proteins, Drosophila, Germ cell, Actin, Developmental Biology
Abstract

The RNA-binding protein Lark has an essential maternal role during Drosophila oogenesis. Elimination of maternal expression results in defects in cytoplasmic dumping and actin cytoskeletal organization in nurse cells. The function of this protein is dependent on the activity of one or more N-terminal RNA-binding domains. Here, we report the identification of Dmoesin (Dmoe) as a candidate RNA target of Lark during oogenesis. In addition to actin defects in the nurse cells of lark mutant ovaries, we observed mislocalization of posteriorly localized mRNAs including oskar and germ cell less in the developing oocyte. Anteriorly and dorsally localized mRNAs were not affected. In addition, we observed displacement of the actin cytoskeleton from the oocyte plasma membrane. These phenotypes are reminiscent of mutations in Dmoe and suggested that this RNA maybe a potential target of Lark. We observed a significant decrease in Dmoe protein associated with the membrane of the developing oocyte with no changes in expression or localization within the nurse cells. Evidence for an association between Lark protein and moe RNA during oogenesis comes from results of a microarray-based Ribonomics approach to identify Lark RNA targets. Thus, our results provide evidence that Dmoe RNA is a target of Lark during oogenesis and that it likely regulates either the splicing or translation of this RNA.

Published
2008
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9. A Bioinformatics Course‐based Undergraduate Research Experience

Author

Gerard P. McNeil, Wilson Leung, David Lopatto, Christopher D. Shaffer, Sarah C. R. Elgin, and Ken Saville

Subjects
0303 health sciences, 03 medical and health sciences, Medical education, 0302 clinical medicine, Undergraduate research, Genetics, Psychology, Molecular Biology, Biochemistry, 030217 neurology & neurosurgery, 030304 developmental biology, Biotechnology, Course (navigation)
Published
2015
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10. Translational Regulation of the DOUBLETIME/CKIÎ'/É> Kinase by LARK Contributes to Circadian Period Modulation

Author

F. Rob Jackson, Gerard P. McNeil, and Yanmei Huang

Subjects
Cancer Research, Light, Casein Kinase 1 epsilon, Circadian clock, Gene Expression, Doubletime, Biochemistry, Behavioral Neuroscience, Cell Signaling, Translational regulation, Molecular Cell Biology, Drosophila Proteins, Genetics (clinical), Genetics, Drosophila Melanogaster, RNA-Binding Proteins, Period Circadian Proteins, Animal Models, Darkness, Circadian Rhythm, Insects, Hippo signaling, Perspective, Drosophila, Research Article, Signal Transduction, lcsh:QH426-470, Arthropoda, Period (gene), Biology, Research and Analysis Methods, Model Organisms, Circadian Clocks, Animals, Circadian rhythm, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Alleles, Organisms, Biology and Life Sciences, Cell Biology, Casein Kinase Iepsilon, Invertebrates, lcsh:Genetics, Gene Expression Regulation, Protein Biosynthesis, Protein Translation, Gene Function, Molecular Neuroscience, Neuroscience
Abstract

The Drosophila homolog of Casein Kinase I δ/ε, DOUBLETIME (DBT), is required for Wnt, Hedgehog, Fat and Hippo signaling as well as circadian clock function. Extensive studies have established a critical role of DBT in circadian period determination. However, how DBT expression is regulated remains largely unexplored. In this study, we show that translation of dbt transcripts are directly regulated by a rhythmic RNA-binding protein (RBP) called LARK (known as RBM4 in mammals). LARK promotes translation of specific alternative dbt transcripts in clock cells, in particular the dbt-RC transcript. Translation of dbt-RC exhibits circadian changes under free-running conditions, indicative of clock regulation. Translation of a newly identified transcript, dbt-RE, is induced by light in a LARK-dependent manner and oscillates under light/dark conditions. Altered LARK abundance affects circadian period length, and this phenotype can be modified by different dbt alleles. Increased LARK delays nuclear degradation of the PERIOD (PER) clock protein at the beginning of subjective day, consistent with the known role of DBT in PER dynamics. Taken together, these data support the idea that LARK influences circadian period and perhaps responses of the clock to light via the regulated translation of DBT. Our study is the first to investigate translational control of the DBT kinase, revealing its regulation by LARK and a novel role of this RBP in Drosophila circadian period modulation., Author Summary The CKI family of serine/threonine kinase regulates diverse cellular processes, through binding to and phosphorylation of a variety of protein substrates. In mammals, mutations in two members of the family, CKIε and CKIδ were found to affect circadian period length, causing phenotypes such as altered circadian period in rodents and the Familial Advanced Sleep Phase Syndrome (FASPS) in human. The Drosophila CKI δ/ε homolog DOUBLETIME (DBT) is known to have important roles in development and circadian clock function. Despite extensive studies of DBT function, little is known about how its expression is regulated. In a previous genome-wide study, we identified dbt mRNAs as potential targets of the LARK RBP. Here we describe a detailed study of the regulation of DBT expression by LARK. We found that LARK binds to and regulates translation of dbt mRNA, promoting expression of a smaller isoform; we suggest this regulatory mechanism contributes to circadian period determination. In addition, we have identified a dbt mRNA that exhibits light-induced changes in translational status, in a LARK-dependent manner. Our study is the first to analyze the translational regulation of DBT, setting the stage for similar studies in other contexts and model systems.

Published
2014

11. A central support system can facilitate implementation and sustainability of a Classroom-based Undergraduate Research Experience (CURE) in Genomics

Author

Lisa Kadlec, Vidya Chandrasekaran, Michael R. Rubin, Aparna Sreenivasan, Srebrenka Robic, David Dunbar, Christopher D. Shaffer, Amy Frary, Sarah C. R. Elgin, Charles R. Hauser, Gerard P. McNeil, Michael J. Wolyniak, Jane Lopilato, Shubha Govind, Chunguang Du, Gary A Kuleck, Martin G. Burg, Justin R. DiAngelo, Julia A. Emerson, Jennifer A Roecklien-Canfield, Kenneth Saville, Adam Haberman, Alexis Nagengast, Susan Parrish, David Lopatto, James J. Youngblom, Wilson Leung, Laura D Reed, Nighat P. Kokan, Olga R. Kopp, Amy T. Hark, Arlene J. Hoogewerf, Mary Spratt, Yuying Gosser, Elaine R. Mardis, James E. J. Bedard, John M. Braverman, April E. Bednarski, Christy MacKinnon, Karim A. Sharif, Christopher D. Smith, Diana L. E. Johnson, Satish C. Bhalla, Marian M. Kaehler, Daron C. Barnard, Jeremy Buhler, Donald R. Frohlich, S. Catherine Silver Key, Randall J. DeJong, Stephanie F. Mel, Paul J. Overvoorde, Consuelo J. Alvarez, Jeffrey S. Thompson, Don W. Paetkau, Dennis Revie, Mary A. Smith, Mary Shaw, Todd T. Eckdahl, Joyce Stamm, Hui-Min Chung, Juan Carlos Martínez-Cruzado, Christopher J. Jones, Gary R. Skuse, Anya Goodman, Mary L. Preuss, Leming Zhou, Eric P. Spana, Anne G. Rosenwald, Matthew Wawersik, Jennifer Mary Threlfall, Stephanie Schroeder, Sheryl T. Smith, E. Gloria C. Regisford, and Dolan, Erin

Subjects
Value (ethics), Models, Educational, Universities, Genomics, Articles, General Biochemistry, Genetics and Molecular Biology, United States, Education, Incentive, Undergraduate research, Models, Clinical Research, General partnership, Pedagogy, Sustainability, ComputingMilieux_COMPUTERSANDEDUCATION, Curriculum development, Engineering ethics, Educational, Curriculum, Program Development, Curriculum and Pedagogy
Abstract

There have been numerous calls to engage students in science as science is done. A survey of 90-plus faculty members explores barriers and incentives when developing a research-based genomics course. The results indicate that a central core supporting a national experiment can help overcome local obstacles., In their 2012 report, the President's Council of Advisors on Science and Technology advocated “replacing standard science laboratory courses with discovery-based research courses”—a challenging proposition that presents practical and pedagogical difficulties. In this paper, we describe our collective experiences working with the Genomics Education Partnership, a nationwide faculty consortium that aims to provide undergraduates with a research experience in genomics through a scheduled course (a classroom-based undergraduate research experience, or CURE). We examine the common barriers encountered in implementing a CURE, program elements of most value to faculty, ways in which a shared core support system can help, and the incentives for and rewards of establishing a CURE on our diverse campuses. While some of the barriers and rewards are specific to a research project utilizing a genomics approach, other lessons learned should be broadly applicable. We find that a central system that supports a shared investigation can mitigate some shortfalls in campus infrastructure (such as time for new curriculum development, availability of IT services) and provides collegial support for change. Our findings should be useful for designing similar supportive programs to facilitate change in the way we teach science for undergraduates.

Published
2014
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12. An Extraretinally Expressed Insect Cryptochrome with Similarity to the Blue Light Photoreceptors of Mammals and Plants

Author

Marla J. Hilderbrand-Chae, Elizabeth S. Egan, Xiaolan Zhang, Gerard P. McNeil, F. Rob Jackson, Andrew J. Schroeder, Mary A. Roberts, and Tina M. Franklin

Subjects
genetic structures, Molecular Sequence Data, Photosynthetic Reaction Center Complex Proteins, Genes, Insect, In situ hybridization, Biology, Gene dosage, Article, Receptors, G-Protein-Coupled, Mice, Cryptochrome, Biological Clocks, Oscillometry, medicine, Animals, Drosophila Proteins, Humans, Amino Acid Sequence, RNA, Messenger, Circadian rhythm, Eye Proteins, Gene, Genetics, Retina, Flavoproteins, Sequence Homology, Amino Acid, General Neuroscience, fungi, Brain, Chromosome Mapping, Circadian Rhythm, Cell biology, Cryptochromes, medicine.anatomical_structure, Insect Proteins, Drosophila, Photoreceptor Cells, Invertebrate, sense organs, Drosophila Protein, Visual phototransduction
Abstract

Photic entrainment of insect circadian rhythms can occur through either extraretinal (brain) or retinal photoreceptors, which mediate sensitivity to blue light or longer wavelengths, respectively. Although visual transduction processes are well understood in the insect retina, almost nothing is known about the extraretinal blue light photoreceptor of insects. We now have identified and characterized a candidate blue light photoreceptor gene inDrosophila(DCry) that is homologous to the cryptochrome (Cry) genes of mammals and plants. TheDCrygene is located in region 91F of the third chromosome, an interval that does not contain other genes required for circadian rhythmicity. The protein encoded byDCryis ∼50% identical to the CRY1 and CRY2 proteins recently discovered in mammalian species. As expected for an extraretinal photoreceptor mediating circadian entrainment,DCrymRNA is expressed within the adult brain and can be detected within body tissues. Indeed, tissuein situhybridization demonstrates prominent expression in cells of the lateral brain, which are close to or coincident with theDrosophilaclock neurons. Interestingly,DCrymRNA abundance oscillates in a circadian manner inDrosophilahead RNA extracts, and the temporal phasing of the rhythm is similar to that documented for the mouseCry1mRNA, which is expressed in clock tissues. Finally, we show that changes inDCrygene dosage are associated predictably with alterations of the blue light resetting response for the circadian rhythm of adult locomotor activity.

Published
1999
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13. Assignment of the Nuclear Mitotic Apparatus Protein NuMA Gene to Human Chromosome 11q13

Author

Gerard P. McNeil, Jeanne B. Lawrence, Edward G. Fey, Peter Lawrence Bangs, and Cynthia A. Sparks

Subjects
DNA, Complementary, Chromosomes, Human, Pair 11, Antibodies, Monoclonal, Chromosome Mapping, Nuclear Proteins, Chromosome, Antigens, Nuclear, Cell Cycle Proteins, Biology, Nuclear matrix, Molecular biology, Spindle apparatus, Genes, Nuclear Matrix-Associated Proteins, Complementary DNA, Genetics, Humans, Sister chromatids, Nuclear protein, Mitosis, Gene, In Situ Hybridization, Fluorescence
Abstract

A monoclonal antibody that was specific for a nuclear matrix protein was obtained and used to screen a human λgt11 expression library. Several partial cDNA clones were isolated and sequenced. The sequence for this protein was shown to be identical to that of NuMA, a 236-kDa nuclear mitotic spindle apparatus protein. NuMA has been recently characterized by two independent studies, and is thought to be part of a family of proteins that is required for the completion of mitosis. In this report, the chromosomal localization and copy number of the NuMA gene are analyzed using cDNA clones. High-resolution in situ hybridization reveals a single pair of signals on sister chromatids of human chromosome 11 at band q13. Stringent Southern analysis of human genomic DNA resulted in simple restriction patterns. These results together indicate that the NuMA gene is present as a single copy on human chromosome 11q13.

Published
1993
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14. Genetic analysis of functional domains within the Drosophila LARK RNA-binding protein

Author

F. Rob Jackson, Andrew J. Schroeder, Gerard P. McNeil, and Mary A. Roberts

Subjects
Male, Time Factors, Mutant, Amino Acid Motifs, Immunoblotting, Molecular Sequence Data, Mutagenesis (molecular biology technique), RNA-binding protein, Biology, medicine.disease_cause, Epitopes, Sex Factors, Genetics, medicine, Animals, Drosophila Proteins, Amino Acid Sequence, Transgenes, Crosses, Genetic, Zinc finger, Mutation, RNA recognition motif, Models, Genetic, RNA-Binding Proteins, Phenotype, Immunohistochemistry, Circadian Rhythm, Protein Structure, Tertiary, Fertility, RNA, Drosophila, Female, Function (biology), Research Article, Protein Binding
Abstract

LARK is an essential Drosophila RNA-binding protein of the RNA recognition motif (RRM) class that functions during embryonic development and for the circadian regulation of adult eclosion. LARK protein contains three consensus RNA-binding domains: two RRM domains and a retroviral-type zinc finger (RTZF). To show that these three structural domains are required for function, we performed a site-directed mutagenesis of the protein. The analysis of various mutations, in vivo, indicates that the RRM domains and the RTZF are required for wild-type LARK functions. RRM1 and RRM2 are essential for viability, although interestingly either domain can suffice for this function. Remarkably, mutation of either RRM2 or the RTZF results in the same spectrum of phenotypes: mutants exhibit reduced viability, abnormal wing and mechanosensory bristle morphology, female sterility, and flightlessness. The severity of these phenotypes is similar in single mutants and double RRM2; RTZF mutants, indicating a lack of additivity for the mutations and suggesting that RRM2 and the RTZF act together, in vivo, to determine LARK function. Finally, we show that mutations in RRM1, RRM2, or the RTZF do not affect the circadian regulation of eclosion, and we discuss possible interpretations of these results. This genetic analysis demonstrates that each of the LARK structural domains functions in vivo and indicates a pleiotropic requirement for both the LARK RRM2 and RTZF domains.

Published
2001

15. Genomics Education Partnership

Author

Jim Youngblom, Kenneth Saville, Chunguang Du, Wilson Leung, Olga R. Kopp, G Regisford, Todd T. Eckdahl, Elaine R. Mardis, Jeffrey S. Thompson, Jennifer Leigh Myka, David Lopatto, Mary A. Smith, Charles R. Hauser, Joyce Stamm, Consuelo J. Alvarez, Chitra Chandrasekaran, Sarah C. R. Elgin, C Witkowski, Daron C. Barnard, Christopher J. Jones, Gary A Kuleck, Paul J. Overvoorde, Gerard P. McNeil, Dennis Revie, Alexis Nagengast, Barbara A. Wilson, Kelynne E. Reed, Christopher D. Shaffer, Jeffrey L. Poet, Mary Spratt, Jeremy Buhler, Anne G. Rosenwald, H-M Chung, Christopher D. Smith, M Shaw, Gary R. Skuse, Anya Goodman, and Robert W. Morris

Subjects
Multidisciplinary, Undergraduate research, Work (electrical), General partnership, education, Pooling, ComputingMilieux_COMPUTERSANDEDUCATION, Genomics, Engineering ethics, Sociology, Engineering physics, health care economics and organizations
Abstract

The Genomics Education Partnership offers an inclusive model for undergraduate research experiences, with students pooling their work to contribute to international databases.

Published
2008
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16. Synergistic activation of neurotensin/neuromedin N gene expression by c-Jun and glucocorticoids: novel effects of Fos family proteins

Author

Gerard P. McNeil, Paul R. Dobner, and Robert W. Harrison

Subjects
Transcriptional Activation, Proto-Oncogene Proteins c-jun, Molecular Sequence Data, DNA Footprinting, Fos-Related Antigen-2, Biology, Regulatory Sequences, Nucleic Acid, PC12 Cells, Dexamethasone, chemistry.chemical_compound, Endocrinology, Receptors, Glucocorticoid, Genes, jun, Gene expression, Lymphocyte costimulation, medicine, Animals, Cyclic AMP Response Element-Binding Protein, Molecular Biology, Gene, Neurotensin, Base Sequence, c-jun, Colforsin, General Medicine, Molecular biology, Peptide Fragments, Rats, DNA-Binding Proteins, Transcription Factor AP-1, Neurotensin/Neuromedin N, chemistry, Gene Expression Regulation, Oligodeoxyribonucleotides, Neuromedin N, Proto-Oncogene Proteins c-fos, Glucocorticoid, medicine.drug, Signal Transduction, Transcription Factors
Abstract

The cis-regulatory region of the neurotensin/neuromedin N (NT/N) gene integrates diverse environmental signals in the neuroendocrine PC12 cell line, resulting in remarkable synergistic regulation. An AP-1 site appears to play a pivotal role in cooperative NT/N gene activation, as mutations in this site decrease responses to all inducer combinations by at least an order of magnitude. Here we report that c-Jun acts synergistically with glucocorticoids to activate the NT/N promoter, and that Fos family proteins have novel regulatory effects on this interaction. Cotransfection of individual pCMV-AP-1 expression plasmids revealed that c-Jun most potently activates the NT/N promoter and that costimulation with dexamethasone results in a further 6- to 12-fold increase in expression. Unlike its general inhibitory effects on glucocorticoid regulation in other systems, c-Fos potentiated activation by glucocorticoids when coexpressed with c-Jun, and Fos B had a similar, but more limited, positive effect. In contrast, Fra-1 reversed the direction of glucocorticoid regulation, and Fra-2 abolished synergism. AP-1, cAMP response element, and glucocorticoid response element motifs are required for full cooperative activation by either c-Jun or c-Jun/c-Fos and glucocorticoids. These results indicate that NT/N promoter activation involves synergistic interactions between specific AP-1 complexes and ligand-activated glucocorticoid receptor, and similar mechanisms may regulate NT/N gene expression in central neurons.

Published
1995

17. A Molecular Rhythm Mediating Circadian Clock Output in Drosophila

Author

Ginka K. Genova, F. Rob Jackson, Xiaolan Zhang, and Gerard P. McNeil

Subjects
Period (gene), Neuroscience(all), Circadian clock, Repressor, Biology, medicine.disease_cause, medicine, Animals, Drosophila Proteins, Circadian rhythm, RNA, Messenger, Gene, Genetics, Neurons, Mutation, Behavior, Animal, General Neuroscience, Neuropeptides, RNA-Binding Proteins, Cell biology, Circadian Rhythm, Phenotype, Darkness, Insect Proteins, Drosophila, Drosophila Protein
Abstract

Analysis of the Drosophila lark gene indicates that it encodes an RNA-binding protein that functions as a regulatory element of the circadian clock output pathway controlling adult eclosion. We now demonstrate that the lark RNA-binding protein oscillates in abundance during the circadian cycle; importantly, the phasing of the lark rhythm is consistent with gene-dosage studies, which indicate that the protein behaves as a repressor molecule. The lark protein rhythm persists in constant conditions (continuous darkness and constant temperature) and is eliminated by period gene null mutations, confirming that it is under clock control and suggesting that it acts as an output mechanism that mediates the temporal regulation of adult eclosion. We also show that lark protein oscillates in abundance within a defined group of neuropeptide (CCAP) -containing neurons of the ventral nervous system (VNS), which in other insects are thought to comprise cellular elements of the clock output pathway regulating eclosion.

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