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1. Student Attitudes Contribute to the Effectiveness of a Genomics CURE

Author

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

Subjects
active learning, bioinformatics, CUREs, genomics, undergraduate education, Special aspects of education, LC8-6691, Biology (General), QH301-705.5
Abstract

ABSTRACT The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student’s epistemic beliefs to achieving positive learning outcomes.

Published
2022
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2. Evaluating the impact of universal Lynch syndrome screening in a publicly funded healthcare system

Author

Petra W. C. Lee, Angela C. Bedard, Setareh Samimi, Vivienne K. Beard, Quan Hong, James E. J. Bedard, Blake Gilks, David F. Schaeffer, Robert Wolber, Janice S. Kwon, Howard J. Lim, Sophie Sun, and Kasmintan A. Schrader

Subjects
colorectal cancer, endometrial cancer, DNA mismatch repair, genetic testing, immunohistochemistry, Lynch syndrome, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Purpose Referrals for Lynch syndrome (LS) assessment have traditionally been based on personal and family medical history. The introduction of universal screening practices has allowed for referrals based on immunohistochemistry tests for mismatch repair (MMR) protein expression. This study aims to characterize the effect of universal screening in a publicly funded healthcare system with comparison to patients referred by traditional criteria, from January 2012 to March 2017. Methods Patient files from the time of initiation of universal screening from 2012 to 2017 were reviewed. Patients were sorted into two groups: (a) universally screened and (b) referred by traditional methods. Mutation detection rates, analysis of traditional testing criteria met, and cascade carrier testing were evaluated. Results The mutation detection rate of the universal screening group was higher than the traditionally referred group (45/228 (19.7%) vs 50/390 (12.5%), P = .05), though each were able to identify unique patients. An analysis of testing criteria met by each patient showed that half of referred patients from the universal screening group could not meet any traditional testing criteria. Conclusion The implementation of universal screening in a publicly funded system will increase efficiency in detecting patients with LS. The resources available for genetic testing and counseling may be more limited in public systems, thus inclusion of secondary screening with BRAF and MLH1 promoter hypermethylation testing is key to further optimizing efficiency.

Published
2020
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3. Facilitating Growth through Frustration: Using Genomics Research in a Course-Based Undergraduate Research Experience

Author

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

Subjects
Special aspects of education, LC8-6691, Biology (General), QH301-705.5
Abstract

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. 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 is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our “formative frustration” hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned 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 “formative frustration” is an important aspect for a successful CURE.

Published
2020
Full Text
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4. Evaluating the impact of universal Lynch syndrome screening in a publicly funded healthcare system

Author

Sophie Sun, Kasmintan A. Schrader, Petra W. C. Lee, Vivienne K. Beard, Howard John Lim, James E. J. Bedard, Janice S. Kwon, David F. Schaeffer, Angela C. Bedard, Blake Gilks, Setareh Samimi, Robert Wolber, and Quan Hong

Subjects
0301 basic medicine, Male, Cancer Research, Financing, Government, National Health Programs, DNA mismatch repair, Cost-Benefit Analysis, DNA Mutational Analysis, 0302 clinical medicine, Early Detection of Cancer, Original Research, medicine.diagnostic_test, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Lynch syndrome, Oncology, 030220 oncology & carcinogenesis, endometrial cancer, immunohistochemistry, Female, Healthcare system, Primary screening, medicine.medical_specialty, colorectal cancer, Carrier testing, lcsh:RC254-282, genetic testing, 03 medical and health sciences, Promoter hypermethylation, Predictive Value of Tests, medicine, Biomarkers, Tumor, Humans, Radiology, Nuclear Medicine and imaging, Medical history, Mutation detection, Genetic Predisposition to Disease, Genetic testing, Public Sector, British Columbia, business.industry, Clinical Cancer Research, Reproducibility of Results, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, 030104 developmental biology, DNA Repair Enzymes, Family medicine, Mutation, business
Abstract

Purpose Referrals for Lynch syndrome (LS) assessment have traditionally been based on personal and family medical history. The introduction of universal screening practices has allowed for referrals based on immunohistochemistry tests for mismatch repair (MMR) protein expression. This study aims to characterize the effect of universal screening in a publicly funded healthcare system with comparison to patients referred by traditional criteria, from January 2012 to March 2017. Methods Patient files from the time of initiation of universal screening from 2012 to 2017 were reviewed. Patients were sorted into two groups: (a) universally screened and (b) referred by traditional methods. Mutation detection rates, analysis of traditional testing criteria met, and cascade carrier testing were evaluated. Results The mutation detection rate of the universal screening group was higher than the traditionally referred group (45/228 (19.7%) vs 50/390 (12.5%), P = .05), though each were able to identify unique patients. An analysis of testing criteria met by each patient showed that half of referred patients from the universal screening group could not meet any traditional testing criteria. Conclusion The implementation of universal screening in a publicly funded system will increase efficiency in detecting patients with LS. The resources available for genetic testing and counseling may be more limited in public systems, thus inclusion of secondary screening with BRAF and MLH1 promoter hypermethylation testing is key to further optimizing efficiency., Lynch syndrome detection rates were higher in a universal screening cohort as compared to those referred by traditional phenotypic‐based referral criteria. Optimizing efficiency for Lynch syndrome screening is important in publicly funded systems where genetic counseling and other resources may be limited.

Published
2020

5. Student Attitudes Contribute to the Effectiveness of a Genomics CURE

Author

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

Subjects
General Immunology and Microbiology, General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Education
Abstract

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student's epistemic beliefs to achieving positive learning outcomes.

Published
2021

6. Patient ethnicity and cascade genetic testing: a descriptive study of a publicly funded hereditary cancer program

Author

Eryn F, Braley, Angela C, Bedard, Jennifer, Nuk, Quan, Hong, James E J, Bedard, Sophie, Sun, and Kasmintan A, Schrader

Subjects
Male, Genes, BRCA2, Ethnicity, Humans, Female, Genetic Predisposition to Disease, Genetic Testing, Middle Aged, Colorectal Neoplasms, Hereditary Nonpolyposis
Abstract

Cascade genetic testing for hereditary cancer is highly accurate and cost-effective for identifying individuals at high risk for cancer; however, not all eligible people utilize this service. While sociodemographic factors related to the uptake of cascade genetic testing, such as age and sex, have been fairly well described in the literature, there is limited data available regarding patient ethnicity. We analyzed four years of testing data for this factor, as well as sex, age and genes tested. The patients were seen by the Hereditary Cancer Program of BC Cancer, which serves the entire population of British Columbia and Yukon, Canada. Patient ethnicity was compared to the 2016 Census data from the same region. Fisher's exact test was conducted to explore the cascade genetic testing uptakes. Chi-square test was used to compare the major ethnicity groups to Census data. There was significant variability in the uptake of cascade genetic testing in the three largest population groups (p 0.05), with individuals of European ethnic origin overrepresented, individuals of Asian ethnic origin modestly underrepresented, and individuals of North American Indigenous origin considerably underrepresented for cascade genetic testing. The proportions represented compared to those expected from census data were significantly different for these three largest groups (p 0.01). The majority of cascade genetic tests were for BRCA1/BRCA2 (58.8%), followed by 16.9% for Lynch syndrome genes. Most patients were female (70%), and the mean age of patients was 49 years old. This study provides further insight into uptake of cascade genetic testing by patient ethnicity. Examining patient ethnicity and cascade genetic testing rates helps to identify underserved populations. Our analysis highlights significant underrepresentation of North American Indigenous individuals for hereditary cancer cascade genetic testing, and helps recognize the need for development of culturally-safe alternatives to outreach and service promotion.

Published
2021

7. Genetic testing in families with hereditary colorectal cancer in British Columbia and Yukon: a retrospective cross-sectional analysis

Author

Kasmintan A. Schrader, Vivienne K. Beard, Jennifer Nuk, Petra W. C. Lee, James E. J. Bedard, Angela C. Bedard, Quan Hong, and Sophie Sun

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, Colorectal cancer, Population, Carrier testing, MLH1, Familial adenomatous polyposis, Young Adult, Internal medicine, Yukon Territory, medicine, Humans, Family, Genetic Predisposition to Disease, Genetic Testing, education, Genetic testing, Aged, Retrospective Studies, education.field_of_study, medicine.diagnostic_test, British Columbia, business.industry, Research, Cancer, General Medicine, Middle Aged, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Lynch syndrome, Cross-Sectional Studies, Adenomatous Polyposis Coli, Female, business
Abstract

Background Genetic testing in families with hereditary cancer enables identification of people most likely to benefit from intensive screening and preventive measures; however, the uptake of testing in relatives (known as cascade carrier testing) for hereditary colorectal cancer syndromes has been shown to be low. Our objective was to report rates of familial testing for hereditary colorectal cancer syndromes in a publicly funded hereditary cancer clinic in Canada. Methods A cross-sectional retrospective database review was used to determine testing uptake between 1997 and 2016 for families served by the provincial Hereditary Cancer Program for British Columbia and Yukon. Analyses were conducted for genes associated with syndromes with an increased risk for colorectal cancer, including Lynch syndrome (MLH1, MSH2, MSH6, PMS2 and EPCAM) and familial adenomatous polyposis (APC), and for additional moderate- to high-penetrance genes (STK11, TP53, SMAD4, MUTYH, PTEN and CHEK2). Descriptive statistics were used and all analyses were 2-tailed. Results The study cohort included 245 index patients, with carrier testing performed in 382 relatives. The mean age at family member testing was 41.2 years, and most (61.0%) of the family members who underwent testing were women. The median time between disclosure of index cases and their family member's results was 8.3 months. Among eligible first-degree relatives, 32.6% (268/821) underwent testing in BC. Of 67 cancer diagnoses in family members, most (62.7%) occurred before genetic testing. Interpretation A substantial proportion of people at risk for hereditary colorectal cancer do not undergo genetic testing. This gap highlights the need to explore barriers to testing and to consider interventions to promote uptake; more aggressive efforts by hereditary cancer programs are needed to reach this highest risk population.

Published
2020

8. 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

9. 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

10. 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

11. Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3

Author

Jennifer D. Purnell, James E. J. Bedard, and Stephanie M. Ware

Subjects
Blotting, Western, Molecular Sequence Data, Nuclear Localization Signals, Active Transport, Cell Nucleus, Oligonucleotides, Importin, Biology, Mice, Species Specificity, Genetics, Animals, Humans, NLS, Amino Acid Sequence, Luciferases, Nuclear export signal, Molecular Biology, Genetics (clinical), Homeodomain Proteins, Nuclear Export Signals, Zinc finger transcription factor, Zinc finger, Binding Sites, Models, Genetic, Point mutation, Computational Biology, General Medicine, Immunohistochemistry, Protein Structure, Tertiary, Cell biology, Mutagenesis, Site-Directed, NIH 3T3 Cells, Nuclear transport, Nuclear localization sequence, HeLa Cells, Signal Transduction, Transcription Factors
Abstract

Missense, frameshift and nonsense mutations in the zinc finger transcription factor ZIC3 cause heterotaxy as well as isolated congenital heart disease. Previously, we developed transactivation and subcellular localization assays to test the function of ZIC3 point mutations. Aberrant cytoplasmic localization suggested that the pathogenesis of ZIC3 mutations results, at least in part, from failure of appropriate cellular trafficking. To further investigate this hypothesis, the nucleocytoplasmic shuttling properties of ZIC3 have been examined. Subcellular localization assays designed to span the entire open-reading frame of wild-type and mutant ZIC3 proteins identified the presence of nucleocytoplasmic transport signals. ZIC3 domain mapping indicates that a relatively large region containing the zinc finger binding sites and a known GLI interacting domain is required for transport to the nucleus. Site-directed mutagenesis of critical residues within two putative nuclear localization signals (NLSs) leads to loss of nuclear localization. No further decrease was observed when both NLS sites were mutated, suggesting that mutation of either NLS site is sufficient for loss of importin-mediated nuclear localization. Additionally, we identify a cryptic CRM-1-dependent nuclear export signal (NES) within ZIC3, and identify a mutation within this region in a patient with heterotaxy. These results provide the first evidence that control of cellular trafficking of ZIC3 is critical for function and suggest a possible mechanism for transcriptional control during left-right patterning. Identification of mutations in mapped NLS or NES domains in heterotaxy patients demonstrates the functional importance of these domains in cardiac morphogenesis and allows for integration of structural analysis with developmental function.

Published
2006

12. 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

13. Identification of a novel ZIC3 isoform and mutation screening in patients with heterotaxy and congenital heart disease

Author

Stephanie M. Ware, Allison Haaning, and James E. J. Bedard

Subjects
Male, Heart malformation, Gene Identification and Analysis, lcsh:Medicine, Dextrocardia, Heterotaxy Syndrome, Cardiovascular, medicine.disease_cause, Gene Splicing, Mice, Exon, 0302 clinical medicine, Protein Isoforms, lcsh:Science, Zinc finger, Genetics, 0303 health sciences, Mutation, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Congenital Heart Disease, Genetic Diseases, X-Linked, Zinc Fingers, Exons, Medicine, Female, Research Article, Gene isoform, Molecular Sequence Data, Biology, Molecular Genetics, 03 medical and health sciences, Sequence Homology, Nucleic Acid, GLI3, medicine, Animals, Humans, Amino Acid Sequence, Genetic Testing, 030304 developmental biology, Homeodomain Proteins, Base Sequence, Sequence Homology, Amino Acid, Gene Expression Profiling, Alternative splicing, lcsh:R, Computational Biology, Molecular biology, Mice, Inbred C57BL, Alternative Splicing, NIH 3T3 Cells, lcsh:Q, Heterotaxy, 030217 neurology & neurosurgery, HeLa Cells, Transcription Factors
Abstract

Patients with heterotaxy have characteristic cardiovascular malformations, abnormal arrangement of their visceral organs, and midline patterning defects that result from abnormal left-right patterning during embryogenesis. Loss of function of the transcription factor ZIC3 causes X-linked heterotaxy and isolated congenital heart malformations and represents one of the few known monogenic causes of congenital heart disease. The birth incidence of heterotaxy-spectrum malformations is significantly higher in males, but our previous work indicated that mutations within ZIC3 did not account for the male over-representation. Therefore, cross species comparative sequence alignment was used to identify a putative novel fourth exon, and the existence of a novel alternatively spliced transcript was confirmed by amplification from murine embryonic RNA and subsequent sequencing. This transcript, termed Zic3-B, encompasses exons 1, 2, and 4 whereas Zic3-A encompasses exons 1, 2, and 3. The resulting protein isoforms are 466 and 456 amino acid residues respectively, sharing the first 407 residues. Importantly, the last two amino acids in the fifth zinc finger DNA binding domain are altered in the Zic3-B isoform, indicating a potential functional difference that was further evaluated by expression, subcellular localization, and transactivation analyses. The temporo-spatial expression pattern of Zic3-B overlaps with Zic3-A in vivo, and both isoforms are localized to the nucleus in vitro. Both isoforms can transcriptionally activate a Gli binding site reporter, but only ZIC3-A synergistically activates upon co-transfection with Gli3, suggesting that the isoforms are functionally distinct. Screening 109 familial and sporadic male heterotaxy cases did not identify pathogenic mutations in the newly identified fourth exon and larger studies are necessary to establish the importance of the novel isoform in human disease.

Published
2011

14. Diversity and evolution of 5S rRNA gene family organization in Pythium

Author

Glen R. Klassen, James E. J. Bedard, Arthur W. A. M. de Cock, and Andrew M. Schurko

Subjects
Genetics, Phylogenetic tree, Sequence analysis, Restriction Mapping, RNA, Ribosomal, 5S, Genetic Variation, Pythium, Plant Science, Biology, Ribosomal RNA, DNA, Ribosomal, Evolution, Molecular, Tandem repeat, Phylogenetics, Genetic variation, Gene family, Gene, Ecology, Evolution, Behavior and Systematics, Phylogeny, Biotechnology
Abstract

The 5S rRNA gene family organization among 87 species and varieties of Pythium was investigated to assess evolutionary stability of the two patterns detected and to determine which pattern is likely the ancestral state in the genus. Species with filamentous sporangia (Groups A-C according to the ITS phylogenetic tree for Pythium) had 5S genes linked to the rDNA repeat that were predominantly coded for on the DNA strand opposite to the one with the other rRNA genes ('inverted' orientation). A small group of species with contiguous sporangia (Group D) is related to Groups A-C but had unlinked 5S genes. The main group of species with spherical zoosporangia (Groups E-J) generally had unlinked 5S genes in tandem arrays. The six species in Group K, although they also have spherical sporangia, had linked genes on the same strand as the other rRNA genes 'non-inverted' and most of them had pairs of tandem 5S genes. The evolutionary stability of 5S sequence organization was compared with the stability of morphological characters as interpreted from a phylogeny based on ITS sequence analysis. Features of 5S sequence organization were found to be just as consistent within groups as were the morphological characters. To determine the ancestral type of 5S family organization, a survey of Phytophthora strains was conducted to supply an outgroup reference. The most parsimonious interpretation of the data in this survey yielded the tentative conclusion that the linked condition of the 5S sequences was ancestral.

Published
2005

15. Development of a Species-Specific Probe for Pythium insidiosum and the Diagnosis of Pythiosis

Author

James E. J. Bedard, Leonel Mendoza, Arthur W. A. M. de Cock, Andrew M. Schurko, and Glen R. Klassen

Subjects
Microbiology (medical), biology, Hybridization probe, Nucleic Acid Hybridization, Pythium, Mycology, Pythium insidiosum, biology.organism_classification, Infections, Sensitivity and Specificity, Prototheca wickerhamii, Microbiology, Pythiosis, genomic DNA, Species Specificity, Humans, Restriction fragment length polymorphism, DNA Probes, Ribosomal DNA
Abstract

Pythium insidiosum, the only species in the genus that infects mammals, is the etiological agent of pythiosis, a granulomatous disease characterized by cutaneous and subcutaneous lesions and vascular diseases. Accurate diagnosis of pythiosis and identification of its causal agent are often inconsistent with current immunological diagnostic methods. A species-specific DNA probe was constructed by using a 530-bp HinfI fragment from the ribosomal DNA intergenic spacer of P. insidiosum. When the probe was incubated with dot blots of genomic DNA from 104 Pythium species, it hybridized only to the DNA of P. insidiosum and P. destruens—two species that have been considered conspecific. The probe also hybridized to DNA from 22 P. insidiosum isolates in this study, regardless of their geographic origin or animal host. When tested against genomic DNA from other pathogenic organisms (Aspergillus fumigatus, Basidiobolus ranarum, Conidiobolus coronatus, Lagenidium giganteum, Paracoccidioides brasiliensis, and Prototheca wickerhamii), no cross-hybridization of the probe was detected. The specificity of the probe to hybridize to genomic DNA from all isolates of P. insidiosum and not cross-react with DNA from other Pythium species or pathogens that cause symptoms similar to pythiosis in their hosts makes it a powerful tool for the accurate diagnosis of pythiosis. In addition, the probe has the potential for pathological and environmental diagnostic applications. Pythium insidiosum (11) is the etiological agent of pythiosis, a granulomatous disease that affects animals including equines, canines, felines, cattle, and humans. The symptoms of pythiosis include cutaneous and subcutaneous infections, bone lesions, esophagitis, gastrointestinal diseases, and pulmonary infections. Pythium is a genus in the class Oomycetes in the Kingdom Straminipila (39) that is comprised of over 120 described species (53). However, P. insidiosum is the only species in the genus capable of infecting mammalian hosts, whereas the other species are saprophytic or pathogenic to plants. Results from restriction fragment length polymorphism analysis (46) and sequence analysis (47) revealed three clades of P. insidiosum isolates representing geographical variants or cryptic speciation. Like most Pythium species, P. insidiosum is difficult to identify morphologically. Gomori’s methenamine-silver nitrate stains P. insidiosum hyphae in tissue nonspecifically. In the infected tissues, short, septate hyphae with perpendicular branching are rarely visible, but members of the Zygomycetes have a similar appearance in histological sections (12). Perhaps the most important cultural identification feature is the production of motile biflagellate zoospores (33), but this is relatively nonspecific and may take weeks to observe, and for some

Published
2004

16. Identification of a novel ZIC3 isoform and mutation screening in patients with heterotaxy and congenital heart disease.

Author

James E J Bedard, Allison M Haaning, and Stephanie M Ware

Subjects
Medicine, Science
Abstract

Patients with heterotaxy have characteristic cardiovascular malformations, abnormal arrangement of their visceral organs, and midline patterning defects that result from abnormal left-right patterning during embryogenesis. Loss of function of the transcription factor ZIC3 causes X-linked heterotaxy and isolated congenital heart malformations and represents one of the few known monogenic causes of congenital heart disease. The birth incidence of heterotaxy-spectrum malformations is significantly higher in males, but our previous work indicated that mutations within ZIC3 did not account for the male over-representation. Therefore, cross species comparative sequence alignment was used to identify a putative novel fourth exon, and the existence of a novel alternatively spliced transcript was confirmed by amplification from murine embryonic RNA and subsequent sequencing. This transcript, termed Zic3-B, encompasses exons 1, 2, and 4 whereas Zic3-A encompasses exons 1, 2, and 3. The resulting protein isoforms are 466 and 456 amino acid residues respectively, sharing the first 407 residues. Importantly, the last two amino acids in the fifth zinc finger DNA binding domain are altered in the Zic3-B isoform, indicating a potential functional difference that was further evaluated by expression, subcellular localization, and transactivation analyses. The temporo-spatial expression pattern of Zic3-B overlaps with Zic3-A in vivo, and both isoforms are localized to the nucleus in vitro. Both isoforms can transcriptionally activate a Gli binding site reporter, but only ZIC3-A synergistically activates upon co-transfection with Gli3, suggesting that the isoforms are functionally distinct. Screening 109 familial and sporadic male heterotaxy cases did not identify pathogenic mutations in the newly identified fourth exon and larger studies are necessary to establish the importance of the novel isoform in human disease.

Published
2011
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