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2. Causal and Associational Language in Observational Health Research: A Systematic Evaluation

Author

Haber, Noah A, Wieten, Sarah E, Rohrer, Julia M, Arah, Onyebuchi A, Tennant, Peter WG, Stuart, Elizabeth A, Murray, Eleanor J, Pilleron, Sophie, Lam, Sze Tung, Riederer, Emily, Howcutt, Sarah Jane, Simmons, Alison E, Leyrat, Clémence, Schoenegger, Philipp, Booman, Anna, Dufour, Mi-Suk Kang, O’Donoghue, Ashley L, Baglini, Rebekah, Do, Stefanie, De La Rosa Takashima, Mari, Evans, Thomas Rhys, Rodriguez-Molina, Daloha, Alsalti, Taym M, Dunleavy, Daniel J, Meyerowitz-Katz, Gideon, Antonietti, Alberto, Calvache, Jose A, Kelson, Mark J, Salvia, Meg G, Parra, Camila Olarte, Khalatbari-Soltani, Saman, McLinden, Taylor, Chatton, Arthur, Seiler, Jessie, Steriu, Andreea, Alshihayb, Talal S, Twardowski, Sarah E, Dabravolskaj, Julia, Au, Eric, Hoopsick, Rachel A, Suresh, Shashank, Judd, Nicholas, Peña, Sebastián, Axfors, Cathrine, Khan, Palwasha, Aguirre, Ariadne E Rivera, Odo, Nnaemeka U, Schmid, Ian, and Fox, Matthew P

Subjects
Epidemiology, Public Health, Health Sciences, Humans, Language, Causality, Biomedical Research, association, causal inference, causal language, observational study, Mathematical Sciences, Medical and Health Sciences
Abstract

We estimated the degree to which language used in the high-profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched for and screened 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, 3 reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as none (no causal implication) in 13.8%, weak in 34.2%, moderate in 33.2%, and strong in 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.

Published
2022

3. A Roadmap for the Human Gut Cell Atlas

Author

Zilbauer, Matthias, James, Kylie R., Kaur, Mandeep, Pott, Sebastian, Li, Zhixin, Burger, Albert, Thiagarajah, Jay R., Burclaff, Joseph, Jahnsen, Frode L., Perrone, Francesca, Ross, Alexander D., Matteoli, Gianluca, Stakenborg, Nathalie, Sujino, Tomohisa, Moor, Andreas, Bartolome-Casado, Raquel, Bækkevold, Espen S., Zhou, Ran, Xie, Bingqing, Lau, Ken S., Din, Shahida, Magness, Scott T., Yao, Qiuming, Beyaz, Semir, Arends, Mark, Denadai-Souza, Alexandre, Coburn, Lori A., Gaublomme, Jellert T., Baldock, Richard, Papatheodorou, Irene, Ordovas-Montanes, Jose, Boeckxstaens, Guy, Hupalowska, Anna, Teichmann, Sarah A., Regev, Aviv, Xavier, Ramnik J., Simmons, Alison, Snyder, Michael P., and Wilson, Keith T.

Published
2023
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5. Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study

Author

Patel, Vinod, Mazhar, Zia, Saich, Rebecca, Colleypriest, Ben, Tham, Tony C, Iqbal, Tariq, Kaushik, Vishal, Murugesan, Senthil, Singh, Salil, Weaver, Sean, Preston, Cathryn, Butt, Assad, Smith, Melissa, Basude, Dharamveer, Beale, Amanda, Langlands, Sarah, Direkze, Natalie, Parkes, Miles, Torrente, Franco, De La Revella Negro, Juan, MacDonald, Chris Ewen, Evans, Stephen M, Gunasekera, Anton VJ, Thakur, Alka, Elphick, David, Shenoy, Achuth, Nwokolo, Chuka U, Dhar, Anjan, Cole, Andrew T, Agrawal, Anurag, Bridger, Stephen, Doherty, Julie, Cooper, Sheldon C, de Silva, Shanika, Mowat, Craig, Mayhead, Phillip, Lees, Charlie, Jones, Gareth, Ahmad, Tariq, Hart, James W, Kennedy, Nicholas A, Goodhand, James R, Lin, Simeng, Chanchlani, Neil, Nice, Rachel, McDonald, Timothy J, Bewshea, Claire, Al-Nuaimi, Yusur, Richards, Ellen, Haigh, Richard, Greenish, Huw, Heath, Harry, Gaya, Daniel R, Russell, Richard K, Gervais, Lisa, Dunckley, Paul, Mahmood, Tariq, Banim, Paul JR, Sonwalkar, Sunil, Ghosh, Deb, Phillips, Rosemary H, Azaz, Amer, Sebastian, Shaji, Shenderey, Richard, Armstrong, Lawrence, Bell, Claire, Hariraj, Radhakrishnan, Matthews, Helen, Jafferbhoy, Hasnain, Selinger, Christian P, Zamvar, Veena, De Caestecker, John S, Willmott, Anne, Miller, Richard, Babu, Palani Sathish, Tzivinikos, Christos, Bloom, Stuart L, Chung-Faye, Guy, Croft, Nicholas M, Fell, John ME, Harbord, Marcus, Hart, Ailsa, Hope, Ben, Irving, Peter M, Lindsay, James O, Mawdsley, Joel E, McNair, Alistair, Monahan, Kevin J, Murray, Charles D, Orchard, Timothy, Paul, Thankam, Pollok, Richard, Shah, Neil, Bouri, Sonia, Johnson, Matt W, Modi, Anita, Kabiru, Kasamu Dawa, Baburajan, B K, Bhaduri, Bim, Fagbemi, Andrew Adebayo, Levison, Scott, Limdi, Jimmy K, Watts, Gill, Foley, Stephen, Ramadas, Arvind, MacFaul, George, Mansfield, John, Grellier, Leonie, Morris, Mary-Anne, Tremelling, Mark, Hawkey, Chris, Kirkham, Sian, Charlton, Charles PJ, Rodrigues, Astor, Simmons, Alison, Lewis, Stephen J, Snook, Jonathon, Tighe, Mark, Goggin, Patrick M, De Silva, Aminda N, Lal, Simon, Smith, Mark S, Panter, Simon, Cummings, JR Fraser, Dharmisari, Suranga, Carter, Martyn, Watts, David, Mahmood, Zahid, McLain, Bruce, Sen, Sandip, Pigott, Anna J, Hobday, David, Wesley, Emma, Johnston, Richard, Edwards, Cathryn, Beckly, John, Vani, Deven, Ramakrishnan, Subramaniam, Chaudhary, Rakesh, Trudgill, Nigel J, Cooney, Rachel, Bell, Andy, Prasad, Neeraj, Gordon, John N, Brookes, Matthew J, Li, Andy, Gore, Stephen, Hamilton, Benjamin, Thomas, Amanda, Smith, Rebecca, Roberts, Christopher, Bishara, Maria, and Lees, Charlie W

Published
2024
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7. Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis

Author

Bird-Lieberman, Elizabeth, Fourie, Simona, Johnston, Richard, Joshi, Heman, Mujamdar, Debabrata, Panter, Simon, Patodi, Nishant, Shaji, Sebastian, Tidbury, Jude, Verma, Ajay, Gupta, Tarun, Antanaviciute, Agne, Hyun-Jung Lee, Chloe, Ottakandathil Babu, Rosana, Aulicino, Anna, Christoforidou, Zoe, Siejka-Zielinska, Paulina, O’Brien-Ball, Caitlin, Chen, Hannah, Fawkner-Corbett, David, Geros, Ana Sousa, Bridges, Esther, McGregor, Colleen, Cianci, Nicole, Fryer, Eve, Alham, Nasullah Khalid, Jagielowicz, Marta, Santos, Ana Mafalda, Fellermeyer, Martin, Davis, Simon J., Parikh, Kaushal, Cheung, Vincent, Al-Hillawi, Lulia, Sasson, Sarah, Slevin, Stephanie, Brain, Oliver, Fernandes, Ricardo A., Koohy, Hashem, and Simmons, Alison

Published
2024
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9. HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Author

Akar, Alaa, Flemming, Cornelius, Felix, Flomm, Flosbach, Markus, Jäger, Julia, Jeromin, Niklas, Jung, Johannes, Ohms, Mareike, Reinshagen, Konrad, Rische, Johann, Sagebiel, Adrian, Sandfort, Deborah, Steinert, Fenja, Tomuschat, Christian, Wesche, Jasmin, Shifteh Abedian, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Alberts, Rudi, Alizadeh, Behrooz, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Annese, Vito, Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Bampton, Peter A., Barclay, Murray, Barrett, Jeffrey C., Bethge, Johannes, Bewshea, Claire, Bis, Joshua C., Bitton, Alain, BK, Thelma, Boucher, Gabrielle, Brain, Oliver, Brand, Stephan, Brant, Steven R., Cheon, Jae Hee, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Cooney, Rachel, Croft, Anthony, Daly, Mark J., D'Amato, Mauro, Danese, Silvio, Daryani, Naser Ebrahim, Datta, Lisa Wu, Degenhardt, Frauke, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Drummond, Hazel E., Dubinsky, Marla, Duerr, Richard H., Edwards, Cathryn, Ellinghaus, David, Ellul, Pierre, Esaki, Motohiro, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Franke, Andre, Fuyuno, Yuta, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Goyette, Philippe, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Hold, Georgina L., Hong, Myhunghee, Hu, Xinli, Huang, Hailiang, Hugot, Jean-Pierre, Hui, Ken Y., Imielinski, Marcin, Jazayeri, Omid, Jonaitis, Laimas, Jostins, Luke, Juyal, Garima, Chandra Juyal, Ramesh, Kalla, Rahul, Karlsen, Tom H., Kennedy, Nicholas A., Khan, Mohammed Azam, Kim, Won Ho, Kitazono, Takanari, Kiudelis, Gediminas, Kubo, Michiaki, Kugathasan, Subra, Kupcinskas, Limas, Lamb, Christopher A., de Lange, Katrina M., Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Lewis, Nina, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Luo, Yang, Mahy, Gillian, Malekzadeh, Masoud Mohammad, Malekzadeh, Reza, Mansfield, John, Marriott, Suzie, Massey, Dunecan, Mathew, Christopher G., Matsui, Toshiyuki, McGovern, Dermot P.B., van der Meulen, Andrea, Midha, Vandana, Milgrom, Raquel, Mirzaei, Samaneh, Mitrovic, Mitja, Montgomery, Grant W., Mowat, Craig, Müller, Christoph, Newman, William G., Ng, Aylwin, Ng, Siew C., Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nöthen, Markus, Oikonomou, Ioannis, Okou, David, Orchard, Timothy R., Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Urõs, Poustchi, Hossein, Prescott, Natalie J., Proctor, Deborah D., Radford-Smith, Graham, Rahier, Jean- Francois, Regueiro, Miguel, Reinisch, Walter, Rieder, Florian, Rioux, John D., Roberts, Rebecca, Rogler, Gerhard, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Scharl, Michael, Schembri, John, Schreiber, Stefan, Schumm, L. Philip, Scott, Regan, Seielstad, Mark, Shah, Tejas, Sharma, Yashoda, Silverberg, Mark S., Simmons, Alison, Simms, Lisa A., Singh, Abhey, Skieceviciene, Jurgita, van Sommeren, Suzanne, Song, Kyuyoung, Sood, Ajit, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sung, Joseph J.Y., Targan, Stephan R., Taylor, Kirstin M., Theatre, Emilie, Torkvist, Leif, Torres, Esther A., Tremelling, Mark, Uhlig, Holm H., Umeno, Junji, Vahedi, Homayon, Vasiliauskas, Eric, Velde, Anje ter, Ventham, Nicholas T., Vermeire, Severine, Verspaget, Hein W., De Vos, Martine, Walters, Thomas, Wang, Kai, Wang, Ming-Hsi, Weersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Wong, Sunny H., Xavier, Ramnik J., Yamazaki, Keiko, Yang, Suk-Kyun, Ye, Byong Duk, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wei, Zhao, Hongyu, Zhao, Zhen Z., Baumdick, Martin E., Niehrs, Annika, Schwerk, Maria, Hinrichs, Ole, Jordan-Paiz, Ana, Padoan, Benedetta, Wegner, Lucy H.M., Schloer, Sebastian, Zecher, Britta F., Malsy, Jakob, Joshi, Vinita R., Illig, Christin, Schröder-Schwarz, Jennifer, Möller, Kimberly J., Martin, Maureen P., Yuki, Yuko, Ozawa, Mikki, Sauter, Jürgen, Schmidt, Alexander H., Perez, Daniel, Giannou, Anastasios D., Carrington, Mary, Davis, Randall S., Schumacher, Udo, Sauter, Guido, Huber, Samuel, Puelles, Victor G., Melling, Nathaniel, Altfeld, Marcus, and Bunders, Madeleine J.

Published
2023
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11. Harvard Should Say Less. Maybe All Schools Should

Author

Feldman, Noah and Simmons, Alison

Subjects
Israel-Hamas War, 2023- -- Influence, Affirmative action -- Forecasts and trends, Polarization (Social sciences) -- Forecasts and trends, College admissions -- Forecasts and trends, Neutrality -- Forecasts and trends, Company public relations, Market trend/market analysis, General interest, News, opinion and commentary, Harvard University -- Public relations -- Evaluation
Abstract

Last fall, Harvard University's leadership found itself at the center of a highly public, highly charged fight about taking an official institutional position in connection with the Oct. 7 Hamas [...]

Published
2024

12. Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

Author

Sazonovs, Aleksejs, Stevens, Christine R., Venkataraman, Guhan R., Yuan, Kai, Avila, Brandon, Abreu, Maria T., Ahmad, Tariq, Allez, Matthieu, Ananthakrishnan, Ashwin N., Atzmon, Gil, Baras, Aris, Barrett, Jeffrey C., Barzilai, Nir, Beaugerie, Laurent, Beecham, Ashley, Bernstein, Charles N., Bitton, Alain, Bokemeyer, Bernd, Chan, Andrew, Chung, Daniel, Cleynen, Isabelle, Cosnes, Jacques, Cutler, David J., Daly, Allan, Damas, Oriana M., Datta, Lisa W., Dawany, Noor, Devoto, Marcella, Dodge, Sheila, Ellinghaus, Eva, Fachal, Laura, Farkkila, Martti, Faubion, William, Ferreira, Manuel, Franchimont, Denis, Gabriel, Stacey B., Ge, Tian, Georges, Michel, Gettler, Kyle, Giri, Mamta, Glaser, Benjamin, Goerg, Siegfried, Goyette, Philippe, Graham, Daniel, Hämäläinen, Eija, Haritunians, Talin, Heap, Graham A., Hiltunen, Mikko, Hoeppner, Marc, Horowitz, Julie E., Irving, Peter, Iyer, Vivek, Jalas, Chaim, Kelsen, Judith, Khalili, Hamed, Kirschner, Barbara S., Kontula, Kimmo, Koskela, Jukka T., Kugathasan, Subra, Kupcinskas, Juozas, Lamb, Christopher A., Laudes, Matthias, Lévesque, Chloé, Levine, Adam P., Lewis, James D., Liefferinckx, Claire, Loescher, Britt-Sabina, Louis, Edouard, Mansfield, John, May, Sandra, McCauley, Jacob L., Mengesha, Emebet, Mni, Myriam, Moayyedi, Paul, Moran, Christopher J., Newberry, Rodney D., O’Charoen, Sirimon, Okou, David T., Oldenburg, Bas, Ostrer, Harry, Palotie, Aarno, Paquette, Jean, Pekow, Joel, Peter, Inga, Pierik, Marieke J., Ponsioen, Cyriel Y., Pontikos, Nikolas, Prescott, Natalie, Pulver, Ann E., Rahmouni, Souad, Rice, Daniel L., Saavalainen, Päivi, Sands, Bruce, Sartor, R. Balfour, Schiff, Elena R., Schreiber, Stefan, Schumm, L. Philip, Segal, Anthony W., Seksik, Philippe, Shawky, Rasha, Sheikh, Shehzad Z., Silverberg, Mark S., Simmons, Alison, Skeiceviciene, Jurgita, Sokol, Harry, Solomonson, Matthew, Somineni, Hari, Sun, Dylan, Targan, Stephan, Turner, Dan, Uhlig, Holm H., van der Meulen, Andrea E., Vermeire, Séverine, Verstockt, Sare, Voskuil, Michiel D., Winter, Harland S., Young, Justine, Duerr, Richard H., Franke, Andre, Brant, Steven R., Cho, Judy, Weersma, Rinse K., Parkes, Miles, Xavier, Ramnik J., Rivas, Manuel A., Rioux, John D., McGovern, Dermot P. B., Huang, Hailiang, Anderson, Carl A., and Daly, Mark J.

Published
2022
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14. Embedded EthiCS: Integrating Ethics Broadly Across Computer Science Education

Author

Grosz, Barbara J., Grant, David Gray, Vredenburgh, Kate, Behrends, Jeff, Hu, Lily, Simmons, Alison, and Waldo, Jim

Subjects
Computer Science - Computers and Society
Abstract

Computing technologies have become pervasive in daily life, sometimes bringing unintended but harmful consequences. For students to learn to think not only about what technology they could create, but also about what technology they should create, computer science curricula must expand to include ethical reasoning about the societal value and impact of these technologies. This paper presents Embedded EthiCS, a novel approach to integrating ethics into computer science education that incorporates ethical reasoning throughout courses in the standard computer science curriculum. It thus changes existing courses rather than requiring wholly new courses. The paper describes a pilot Embedded EthiCS program that embeds philosophers teaching ethical reasoning directly into computer science courses. It discusses lessons learned and challenges to implementing such a program across different types of academic institutions., Comment: Manuscript in submission

Published
2018

16. Goblet cell differentiation subgroups in colorectal cancer.

Author

Abdullayeva, Gulnar, Haoyu Liu, Ta-Chun Liu, Simmons, Alison, Novelli, Marco, Huseynova, Irada, Lastun, Viorica L., and Bodmer, Walter

Subjects
CANCER cell differentiation, TREFOIL factors, CELL differentiation, GENE expression, COLORECTAL cancer
Abstract

The poor prognosis of relatively undifferentiated cancers has long been recognized, suggesting that selection against differentiation and in favor of uncontrolled growth is one of the most powerful drivers of cancer progression. Goblet cells provide the mucous surface of the gut, and when present in colorectal cancers (CRC), the cancers are called mucinous. We have used the presence of MUC2, the main mucous product of goblet cells, and an associated gene product, TFF3, to classify a large panel of nearly 80 CRC-derived cell lines into five categories based on their levels of MUC2 and TFF3 expression. We have then shown that these five patterns of expression can be easily identified in the direct analysis of tumor specimens allowing a much finer characterization of CRCs with respect to the presence of goblet cell differentiation. In particular, about 30% of all CRCs fall into the category of expressing TFF3 but not MUC2, which has not previously been acknowledged. Using the cell line data, we suggest that there are up to 12 genes (MUC2, TFF3, ATOH1, SPDEF, CDX1, CDX2, GATA6, HES1, ETS2, OLFM4, TOX3, and LGR5) that may be involved in selection against goblet cell differentiation in CRC by changes in methylation rather than mutations. Of these, LGR5, which is particularly associated with lack of goblet cell features, may function in the control of differentiation rather than direct control of cell growth, as has so far mostly been assumed. These results emphasize the importance of methylation changes in driving cancer progression [ABSTRACT FROM AUTHOR]

Published
2024
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17. Respiratory syncytial virus vaccination strategies for older Canadian adults: a cost–utility analysis.

Author

Tuite, Ashleigh R., Simmons, Alison E., Rudd, Monica, Cernat, Alexandra, Gebretekle, Gebremedhin B., Yeung, Man Wah, Killikelly, April, Siu, Winnie, Buchan, Sarah A., Brousseau, Nicholas, and Tunis, Matthew

Subjects
*OLDER people, *RESPIRATORY syncytial virus infections, *RESPIRATORY syncytial virus infection vaccines, *CANADIANS, *RESPIRATORY syncytial virus
Abstract

Background: Respiratory syncytial virus (RSV) vaccines could reduce disease burden and costs in older Canadian adults, but vaccination program cost-effectiveness is unknown. We evaluated the cost-effectiveness of different age cut-offs for RSV adult vaccination programs, with or without a focus on people with higher disease risk due to chronic medical conditions. Methods: We developed a static individual-based model of medically attended RSV disease to compare alternative age-, medical risk–, and age-plus medical risk–based vaccination policies. The model followed a multiage population of 100 000 people aged 50 years and older. Vaccine characteristics were based on RSV vaccines authorized in Canada as of May 2024, with vaccine protection assumed to last 2 years (or 3 years in scenario analyses). We calculated sequential incremental cost-effectiveness ratios in 2023 Canadian dollars per quality-adjusted life year (QALY) from the health-system and societal perspectives, discounted at 1.5%. Results: Although all vaccination strategies averted medically attended RSV disease, universal age-based strategies were not an efficient use of resources compared with medical risk–based strategies. Vaccinating adults aged 70 years and older with 1 or more chronic medical condition was the optimal strategy for a cost-effectiveness threshold of $50 000 per QALY. Results were sensitive to assumptions about vaccine price, but medical risk–based approaches remained optimal compared with age-based strategies, even when vaccine prices were low. Findings were robust to a range of alternative assumptions. Interpretation: Vaccination programs for RSV in some groups of older Canadians with underlying medical conditions are likely cost-effective. These findings can inform the design of vaccination programs. [ABSTRACT FROM AUTHOR]

Published
2024
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18. GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis

Author

Rana, Nitish, Privitera, Giuseppe, Kondolf, Hannah C., Bulek, Katarzyna, Lechuga, Susana, De Salvo, Carlo, Corridoni, Daniele, Antanaviciute, Agne, Maywald, Rebecca L., Hurtado, Alexander M., Zhao, Junjie, Huang, Emina H., Li, Xiaoxia, Chan, E. Ricky, Simmons, Alison, Bamias, Giorgos, Abbott, Derek W., Heaney, Jason D., Ivanov, Andrei I., and Pizarro, Theresa T.

Published
2022
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19. Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis

Author

Gupta, Tarun, primary, Antanaviciute, Agne, additional, Hyun-Jung Lee, Chloe, additional, Ottakandathil Babu, Rosana, additional, Aulicino, Anna, additional, Christoforidou, Zoe, additional, Siejka-Zielinska, Paulina, additional, O’Brien-Ball, Caitlin, additional, Chen, Hannah, additional, Fawkner-Corbett, David, additional, Geros, Ana Sousa, additional, Bridges, Esther, additional, McGregor, Colleen, additional, Cianci, Nicole, additional, Fryer, Eve, additional, Alham, Nasullah Khalid, additional, Jagielowicz, Marta, additional, Santos, Ana Mafalda, additional, Fellermeyer, Martin, additional, Davis, Simon J., additional, Parikh, Kaushal, additional, Cheung, Vincent, additional, Al-Hillawi, Lulia, additional, Sasson, Sarah, additional, Slevin, Stephanie, additional, Brain, Oliver, additional, Bird-Lieberman, Elizabeth, additional, Fourie, Simona, additional, Johnston, Richard, additional, Joshi, Heman, additional, Mujamdar, Debabrata, additional, Panter, Simon, additional, Patodi, Nishant, additional, Shaji, Sebastian, additional, Tidbury, Jude, additional, Verma, Ajay, additional, Fernandes, Ricardo A., additional, Koohy, Hashem, additional, and Simmons, Alison, additional

Published
2024
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20. Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study

Author

Chanchlani, Neil, primary, Lin, Simeng, additional, Bewshea, Claire, additional, Hamilton, Benjamin, additional, Thomas, Amanda, additional, Smith, Rebecca, additional, Roberts, Christopher, additional, Bishara, Maria, additional, Nice, Rachel, additional, Lees, Charlie W, additional, Sebastian, Shaji, additional, Irving, Peter M, additional, Russell, Richard K, additional, McDonald, Timothy J, additional, Goodhand, James R, additional, Ahmad, Tariq, additional, Kennedy, Nicholas A, additional, Patel, Vinod, additional, Mazhar, Zia, additional, Saich, Rebecca, additional, Colleypriest, Ben, additional, Tham, Tony C, additional, Iqbal, Tariq, additional, Kaushik, Vishal, additional, Murugesan, Senthil, additional, Singh, Salil, additional, Weaver, Sean, additional, Preston, Cathryn, additional, Butt, Assad, additional, Smith, Melissa, additional, Basude, Dharamveer, additional, Beale, Amanda, additional, Langlands, Sarah, additional, Direkze, Natalie, additional, Parkes, Miles, additional, Torrente, Franco, additional, De La Revella Negro, Juan, additional, MacDonald, Chris Ewen, additional, Evans, Stephen M, additional, Gunasekera, Anton VJ, additional, Thakur, Alka, additional, Elphick, David, additional, Shenoy, Achuth, additional, Nwokolo, Chuka U, additional, Dhar, Anjan, additional, Cole, Andrew T, additional, Agrawal, Anurag, additional, Bridger, Stephen, additional, Doherty, Julie, additional, Cooper, Sheldon C, additional, de Silva, Shanika, additional, Mowat, Craig, additional, Mayhead, Phillip, additional, Lees, Charlie, additional, Jones, Gareth, additional, Hart, James W, additional, Chanchlani, Neil, additional, Al-Nuaimi, Yusur, additional, Richards, Ellen, additional, Haigh, Richard, additional, Greenish, Huw, additional, Heath, Harry, additional, Gaya, Daniel R, additional, Gervais, Lisa, additional, Dunckley, Paul, additional, Mahmood, Tariq, additional, Banim, Paul JR, additional, Sonwalkar, Sunil, additional, Ghosh, Deb, additional, Phillips, Rosemary H, additional, Azaz, Amer, additional, Shenderey, Richard, additional, Armstrong, Lawrence, additional, Bell, Claire, additional, Hariraj, Radhakrishnan, additional, Matthews, Helen, additional, Jafferbhoy, Hasnain, additional, Selinger, Christian P, additional, Zamvar, Veena, additional, De Caestecker, John S, additional, Willmott, Anne, additional, Miller, Richard, additional, Babu, Palani Sathish, additional, Tzivinikos, Christos, additional, Bloom, Stuart L, additional, Chung-Faye, Guy, additional, Croft, Nicholas M, additional, Fell, John ME, additional, Harbord, Marcus, additional, Hart, Ailsa, additional, Hope, Ben, additional, Lindsay, James O, additional, Mawdsley, Joel E, additional, McNair, Alistair, additional, Monahan, Kevin J, additional, Murray, Charles D, additional, Orchard, Timothy, additional, Paul, Thankam, additional, Pollok, Richard, additional, Shah, Neil, additional, Bouri, Sonia, additional, Johnson, Matt W, additional, Modi, Anita, additional, Kabiru, Kasamu Dawa, additional, Baburajan, B K, additional, Bhaduri, Bim, additional, Fagbemi, Andrew Adebayo, additional, Levison, Scott, additional, Limdi, Jimmy K, additional, Watts, Gill, additional, Foley, Stephen, additional, Ramadas, Arvind, additional, MacFaul, George, additional, Mansfield, John, additional, Grellier, Leonie, additional, Morris, Mary-Anne, additional, Tremelling, Mark, additional, Hawkey, Chris, additional, Kirkham, Sian, additional, Charlton, Charles PJ, additional, Rodrigues, Astor, additional, Simmons, Alison, additional, Lewis, Stephen J, additional, Snook, Jonathon, additional, Tighe, Mark, additional, Goggin, Patrick M, additional, De Silva, Aminda N, additional, Lal, Simon, additional, Smith, Mark S, additional, Panter, Simon, additional, Cummings, JR Fraser, additional, Dharmisari, Suranga, additional, Carter, Martyn, additional, Watts, David, additional, Mahmood, Zahid, additional, McLain, Bruce, additional, Sen, Sandip, additional, Pigott, Anna J, additional, Hobday, David, additional, Wesley, Emma, additional, Johnston, Richard, additional, Edwards, Cathryn, additional, Beckly, John, additional, Vani, Deven, additional, Ramakrishnan, Subramaniam, additional, Chaudhary, Rakesh, additional, Trudgill, Nigel J, additional, Cooney, Rachel, additional, Bell, Andy, additional, Prasad, Neeraj, additional, Gordon, John N, additional, Brookes, Matthew J, additional, Li, Andy, additional, and Gore, Stephen, additional

Published
2024
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22. Special Education Teachers' Experiences Addressing Mental Health Concerns in Students with Comorbid Disabilities: A Phenomenological Study

Author

Simmons, Alison L and Simmons, Alison L

Abstract

The purpose of this transcendental phenomenological study was to describe the lived experiences of special education teachers in public schools regarding addressing mental health needs in their students experiencing comorbid disabilities. The theory guiding this study was contextual organizational framework as it applies to individual special education teachers addressing comorbid mental health concerns in their students. The research addresses the central research question: What experiences within the organizational context(s) do special education teachers describe with regard to working with special education students with comorbid mental health disorders? All participants were special education teachers in either elementary or secondary schools, who have been chosen purposefully using criterion sampling methods. Data was collected through structured interviews conducted through an online platform and audio recorded. Data was analyzed using a coding system to determine phenomenon between participants. From the data, three themes emerged: (a) mental health impact, (b) lack of resources and training, and (c) professional development. The results of this study provided stakeholders with an increased understanding of special education teachers’ lived experiences with regard to addressing comorbid mental health concerns in their students. Study findings may inform practices and professional development decisions including educational practices with regard to mental health resources.

Published
2024

23. GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis

Author

Rana, Nitish, primary, Privitera, Giuseppe, additional, Kondolf, Hannah C., additional, Bulek, Katarzyna, additional, Lechuga, Susana, additional, De Salvo, Carlo, additional, Corridoni, Daniele, additional, Antanaviciute, Agne, additional, Maywald, Rebecca L., additional, Hurtado, Alexander M., additional, Zhao, Junjie, additional, Huang, Emina H., additional, Li, Xiaoxia, additional, Chan, E. Ricky, additional, Simmons, Alison, additional, Bamias, Giorgos, additional, Abbott, Derek W., additional, Heaney, Jason D., additional, Ivanov, Andrei I., additional, and Pizarro, Theresa T., additional

Published
2024
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28. Epithelial-derived gasdermin D mediates nonlytic IL-1[beta] release during experimental colitis

Author

Bulek, Katarzyna, Zhao, Junjie, Liao, Yun, Rana, Nitish, Corridoni, Daniele, Antanaviciute, Agne, Chen, Xing, Wang, Han, Qian, Wen, Miller-Little, William A., Swaidani, Shadi, Tang, Fangqiang, Willard, Belinda B., McCrae, Keith, Kang, Zizhen, Dubyak, George R., Cominelli, Fabio, Simmons, Alison, Pizarro, Theresa T., and Li, Xiaoxia

Subjects
Thermo Fisher Scientific Inc. -- International economic relations, Inflammation, Ligases, Gastrointestinal diseases, Colitis, Health care industry
Abstract

Gasdermin D (GSDMD) induces pyroptosis via the pore-forming activity of its N-terminal domain, cleaved by activated caspases associated with the release of IL-1[beta]. Here, we report a nonpyroptotic role of full-length GSDMD in guiding the release of IL-1[beta]-containing small extracellular vesicles (sEVs) from intestinal epithelial cells (lECs). In response to caspase-8 inflammasome activation, GSDMD, chaperoned by Cdc37/Hsp90, recruits the E3 ligase, NEDD4, to catalyze polyubiquitination of pro-IL-1[beta], serving as a signal for cargo loading into secretory vesicles. GSDMD and IL-1[beta] colocalize with the exosome markers CD63 and ALIX intracellularly, and GSDMD and NEDD4 are required for release of CD63+ sEVs containing IL-1[beta], GSDMD, NEDD4, and caspase-8. Importantly, increased expression of epithelial-derived GSDMD is observed both in patients with inflammatory bowel disease (IBD) and those with experimental colitis. While GSDMD-dependent release of IL-1[beta]-containing sEVs is detected in cultured colonic explants from colitic mice, GSDMD deficiency substantially attenuates disease severity, implicating GSDMD-mediated release of IL-1[beta] sEVs in the pathogenesis of intestinal inflammation, such as that observed in IBD., Introduction Inflammasomes are the critical platforms that integrate environmental stimuli to initiate appropriate and necessary innate and adaptive immune responses to maintain homeostasis, particularly at mucosal surfaces in organs that [...]

Published
2020
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29. Paracrine signalling by cardiac calcitonin controls atrial fibrogenesis and arrhythmia

Author

Moreira, Lucia M., Takawale, Abhijit, Hulsurkar, Mohit, Menassa, David A., Antanaviciute, Agne, Lahiri, Satadru K., Mehta, Neelam, Evans, Neil, Psarros, Constantinos, Robinson, Paul, Sparrow, Alexander J., Gillis, Marc-Antoine, Ashley, Neil, Naud, Patrice, Barallobre-Barreiro, Javier, Theofilatos, Konstantinos, Lee, Angela, Norris, Mary, Clarke, Michele V., Russell, Patricia K., Casadei, Barbara, Bhattacharya, Shoumo, Zajac, Jeffrey D., Davey, Rachel A., Sirois, Martin, Mead, Adam, Simmons, Alison, Mayr, Manuel, Sayeed, Rana, Krasopoulos, George, Redwood, Charles, Channon, Keith M., Tardif, Jean-Claude, Wehrens, Xander H. T., Nattel, Stanley, and Reilly, Svetlana

Published
2020
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30. Single-cell atlas of colonic CD8+ T cells in ulcerative colitis

Author

Corridoni, Daniele, Antanaviciute, Agne, Gupta, Tarun, Fawkner-Corbett, David, Aulicino, Anna, Jagielowicz, Marta, Parikh, Kaushal, Repapi, Emmanouela, Taylor, Steve, Ishikawa, Dai, Hatano, Ryo, Yamada, Taketo, Xin, Wei, Slawinski, Hubert, Bowden, Rory, Napolitani, Giorgio, Brain, Oliver, Morimoto, Chikao, Koohy, Hashem, and Simmons, Alison

Published
2020
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31. Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?

Author

Cheung, Vincent Ting Fung, Gupta, Tarun, Olsson-Brown, Anna, Subramanian, Sreedhar, Sasson, Sarah Christina, Heseltine, Jonathan, Fryer, Eve, Collantes, Elena, Sacco, Joseph J., Pirmohamed, Munir, Simmons, Alison, Klenerman, Paul, Tuthill, Mark, Protheroe, Andrew S., Chitnis, Meenali, Fairfax, Benjamin Peter, Payne, Miranda Jane, Middleton, Mark Ross, and Brain, Oliver

Published
2020
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33. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study

Author

Patel, Vinod, Mazhar, Zia, Saich, Rebecca, Colleypriest, Ben, Tham, Tony C, Iqbal, Tariq H, Kaushik, Vishal, Murugesan, Senthil, Singh, Salil, Weaver, Sean, Preston, Cathryn, Butt, Assad, Smith, Melissa, Basude, Dharamveer, Beale, Amanda, Langlands, Sarah, Direkze, Natalie, Parkes, Miles, Torrente, Franco, De La Revella Negro, Juan, MacDonald, Chris Ewen, Evans, Stephen M, Gunasekera, Anton V J, Thakur, Alka, Elphick, David, Shenoy, Achuth, Nwokolo, Chuka U, Dhar, Anjan, Cole, Andrew T, Agrawal, Anurag, Bridger, Stephen, Doherty, Julie, Cooper, Sheldon C, de Silva, Shanika, Mowat, Craig, Mayhead, Phillip, Lees, Charlie, Jones, Gareth, Ahmad, Tariq, Hart, James W, Gaya, Daniel R, Russell, Richard K, Gervais, Lisa, Dunckley, Paul, Mahmood, Tariq, Banim, Paul J R, Sonwalkar, Sunil, Ghosh, Deb, Phillips, Rosemary H, Azaz, Amer, Sebastian, Shaji, Shenderey, Richard, Armstrong, Lawrence, Bell, Claire, Hariraj, Radhakrishnan, Matthews, Helen, Jafferbhoy, Hasnain, Selinger, Christian P, Zamvar, Veena, De Caestecker, John S, Willmott, Anne, Miller, Richard, Babu, Palani Sathish, Tzivinikos, Christos, Bloom, Stuart L, Chung-Faye, Guy, Croft, Nicholas M, Fell, John ME, Harbord, Marcus, Hart, Ailsa, Hope, Ben, Irving, Peter M, Lindsay, James O, Mawdsley, Joel E, McNair, Alistair, Monahan, Kevin J, Murray, Charles D, Orchard, Timothy, Paul, Thankam, Pollok, Richard, Shah, Neil, Bouri, Sonia, Johnson, Matt W, Modi, Anita, Kabiru, Kasamu Dawa, Baburajan, B K, Bhaduri, Bim, Fagbemi, Andrew Adebayo, Levison, Scott, Limdi, Jimmy K, Watts, Gill, Foley, Stephen, Ramadas, Arvind, MacFaul, George, Mansfield, John, Grellier, Leonie, Morris, Mary-Anne, Tremelling, Mark, Hawkey, Chris, Kirkham, Sian, Charlton, Charles PJ, Rodrigues, Astor, Simmons, Alison, Lewis, Stephen J, Snook, Jonathon, Tighe, Mark, Goggin, Patrick M, De Silva, Aminda N, Lal, Simon, Smith, Mark S, Panter, Simon, Cummings, J R Fraser, Dharmisari, Suranga, Carter, Martyn, Watts, David, Mahmood, Zahid, McLain, Bruce, Sen, Sandip, Pigott, Anna J, Hobday, David, Wesley, Emma, Johnston, Richard, Edwards, Cathryn, Beckly, John, Vani, Deven, Ramakrishnan, Subramaniam, Chaudhary, Rakesh, Trudgill, Nigel J, Cooney, Rachel, Bell, Andy, Prasad, Neeraj, Gordon, John N, Brookes, Matthew J, Li, Andy, Gore, Stephen, Kennedy, Nicholas A, Heap, Graham A, Green, Harry D, Hamilton, Benjamin, Bewshea, Claire, Walker, Gareth J, Thomas, Amanda, Nice, Rachel, Perry, Mandy H, Chanchlani, Neil, Heerasing, Neel M, Hendy, Peter, Lin, Simeng, Lees, Charlie W, Hart, Ailsa L, Mansfield, John C, Lindsay, James, McDonald, Timothy J, McGovern, Dermot, and Goodhand, James R

Published
2019
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34. Impact of immune evasion, waning and boosting on dynamics of population mixing between a vaccinated majority and unvaccinated minority.

Author

Fisman, David N., Amoako, Afia, Simmons, Alison, and Tuite, Ashleigh R.

Subjects
VACCINATION status, SARS-CoV-2 Omicron variant, BOOSTER vaccines, VACCINATION, POPULATION dynamics, VACCINE effectiveness
Abstract

Background: We previously demonstrated that when vaccines prevent infection, the dynamics of mixing between vaccinated and unvaccinated sub-populations is such that use of imperfect vaccines markedly decreases risk for vaccinated people, and for the population overall. Risks to vaccinated people accrue disproportionately from contact with unvaccinated people. In the context of the emergence of Omicron SARS-CoV-2 and evolving understanding of SARS-CoV-2 epidemiology, we updated our analysis to evaluate whether our earlier conclusions remained valid. Methods: We modified a previously published Susceptible-Infectious-Recovered (SIR) compartmental model of SARS-CoV-2 with two connected sub-populations: vaccinated and unvaccinated, with non-random mixing between groups. Our expanded model incorporates diminished vaccine efficacy for preventing infection with the emergence of Omicron SARS-CoV-2 variants, waning immunity, the impact of prior immune experience on infectivity, "hybrid" effects of infection in previously vaccinated individuals, and booster vaccination. We evaluated the dynamics of an epidemic within each subgroup and in the overall population over a 10-year time horizon. Results: Even with vaccine efficacy as low as 20%, and in the presence of waning immunity, the incidence of COVID-19 in the vaccinated subpopulation was lower than that among the unvaccinated population across the full 10-year time horizon. The cumulative risk of infection was 3–4 fold higher among unvaccinated people than among vaccinated people, and unvaccinated people contributed to infection risk among vaccinated individuals at twice the rate that would have been expected based on the frequency of contacts. These findings were robust across a range of assumptions around the rate of waning immunity, the impact of "hybrid immunity", frequency of boosting, and the impact of prior infection on infectivity in unvaccinated people. Interpretation: Although the emergence of the Omicron variants of SARS-CoV-2 has diminished the protective effects of vaccination against infection with SARS-CoV-2, updating our earlier model to incorporate loss of immunity, diminished vaccine efficacy and a longer time horizon, does not qualitatively change our earlier conclusions. Vaccination against SARS-CoV-2 continues to diminish the risk of infection among vaccinated people and in the population as a whole. By contrast, the risk of infection among vaccinated people accrues disproportionately from contact with unvaccinated people. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Human enteric glia diversity in health and disease: new avenues for the treatment of Hirschsprung disease

Author

Windster, Jonathan D., primary, Kuil, Laura E., additional, Kakiailatu, Naomi J.M., additional, Antanaviciute, Agne, additional, Sacchetti, Andrea, additional, MacKenzie, Katherine C., additional, Peulen-Zink, Joke, additional, Kan, Tsung Wai, additional, Bindels, Eric, additional, de Pater, Emma, additional, Doukas, Michael, additional, Yousefi, Soheil, additional, Barakat, Tahsin Stefan, additional, Meeussen, Conny J.H.M., additional, Sloots, Pim C.E.J., additional, Wijnen, Renee M.H., additional, Parikh, Kaushal B., additional, Boesmans, Werend, additional, Melotte, Veerle, additional, Hofstra, Robert M.W., additional, Simmons, Alison, additional, and Alves, Maria, additional

Published
2023
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36. Adventures in Assessment: Learner-Centered Approaches to Assessment and Evaluation in Adult Literacy, 2000. Volume 12: Experiences with Standards-Based Reform.

Author

System for Adult Basic Education Support, Boston, MA. and Simmons, Alison

Abstract

In this volume of "Adventures in Assessment," an annual literacy education journal, teachers and practitioners write about their experiences with standards-based reform initiatives at the state and national levels. The following seven articles are included: "What Makes a Good Teacher?" (Marie F. Hassett); "Successful Supervision: Three Perspectives" (Caroline Gear, Rebecca Shiffron, and Steve Kurtz); "A Curriculum Project" (Sherry Spaulding); "A Performance Framework for Teaching and Learning with the Equipped for the Future (EFF) Content Standards" (Peggy McGuire); "Connecting the ESOL (English as a Second Language) Framework to Actual Practice" (Roseann Ritter); "Learning from Experience: To TABE (Test of Adult Basic Education) or Not to TABE One Agency's Options" (Bernie Driscoll); and "Learning and Change: A Phase Two North Carolina ESOL Framework Inquiry Project" (Beth Brockman). (KC)

Published
2000

37. Adventures in Assessment: Learner-Centered Approaches to Assessment and Evaluation in Adult Literacy, 1991-1998.

Author

System for Adult Basic Education Support, Boston, MA., McGrail, Loren, Purdom, Laura, Schwartz, Rick, and Simmons, Alison

Abstract

"Adventures in Assessment" is an annual journal of the system for Adult Basic Education Support (SABES), a comprehensive training and technical assistance initiative for adult literacy educators and programs. SABES accomplishes this goal through staff and program development workshops, consultation, mini-courses, mentoring, peer coaching, and other training activities provided by five Regional Support Centers located at community colleges throughout Massachusetts. The first three volumes present a comprehensive view of the state of practice in Massachusetts through articles written by adult literacy practitioners. Volume 1, "Getting Started," includes start-up and intake activities; volume 2, "Ongoing," shares tools for ongoing assessment as part of the learning process; volume 3, "Looking Back, Starting Again," focuses on tools and procedures used at the end of a cycle or term, including self, class, and group evaluation by both teachers and learners. Volume 4 covers a range of interests, and volume 5, "The Tale of the Tools," is dedicated to reflecting on Component 3 tools of alternative assessment. Volume 6, "Responding to the Dream Conference," is dedicated to responses to volumes 1-5. Volume 7, "The Partnership Project," highlights writings from a memtoring project for practitioners intersted in learning about participatory assessment. Volumes 8-11 cover a range of topics, including educational reform, workplace education, learner involvement in asseessment, etc. (MN)

Published
1998

39. Colonic epithelial cell diversity in health and inflammatory bowel disease

Author

Parikh, Kaushal, Antanaviciute, Agne, Fawkner-Corbett, David, Jagielowicz, Marta, Aulicino, Anna, Lagerholm, Christoffer, Davis, Simon, Kinchen, James, Chen, Hannah H., Alham, Nasullah Khalid, Ashley, Neil, Johnson, Errin, Hublitz, Philip, Bao, Leyuan, Lukomska, Joanna, Andev, Rajinder Singh, Björklund, Elisabet, Kessler, Benedikt M., Fischer, Roman, Goldin, Robert, Koohy, Hashem, and Simmons, Alison

Published
2019
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42. Molecular and mechanistic analysis of HIV Nef

Author

Simmons, Alison

Subjects
616.979201
Abstract

The nef gene of HIV is required for complete viral pathogenicity. As an accessory gene with no known paradigm its principle function has been enigmatic. Nef is capable of a variety of in vitro effects including CD4 downregulation, MHC I down regulation, alteration of T cell signalling activity and enhancement of viral infectivity. The effect of Nef on host CD4 T cell signalling paths is intriguing as it is the earliest expressed HIV gene and because HIV replicates to high levels in activated host cells. An effect of Nef on T cell activation state could dictate host T cell fate tipping the balance between productive viral infection and post-integration latency. Although Nef can form in vitro interactions with a variety of T cell signalling proteins in vivo evidence for signalling path activation has been inconclusive mainly due to the limitations of the experimental systems used to address the question. An in vivo role for Nef in alteration of T cell activation state should lead to gene expression changes in the host cell. Large scale gene expression profiling was used to monitor T cell gene expression after controlled expression of Nef using the tetracycline inducible system. Nef induces a widespread transcriptional program in T cells. Comparison of this profile with reference T ceil activation states reveals a strong identity to the gene expression profile of Jurkat activated by anti-CD3 cross-linking. Gene expression profiling was used to explore the mechanism by which Nef mediates this effect. After cyclosporin treatment the profiie was attenuated. A similar effect was observed after Nef expression in Jurkat T cells genetically deficient in ZAP-70 and functionally deficient in TCRÇ. Expression of a mutant defective in a functional SH3 binding domain had a stronger effect on attenuation of gene induction. Thus gene expression profiling demonstrates definitively Nef is capable of activating T cells at the transcriptional level and that this effect is initiated high in the T cell signalling path. Within the Nef expression profile differential expression of multiple genes with the ability to affect virai replication was noted. In a few instances it was possible to demonstrate the Nef mediated changes in mRNA levels were functionally significant. Proteomic analysis of Nef effect on T cells was initiated. 2D gel analysis of T cell lysates after Nef expression demonstrated a differential regulation of proteins in T cell lysates. The mechanism by which Nef initiates T cell signalling was explored using a similar approach. The proteins interacting with Nef in lipid rafts were identified after immunoprécipitation of HA tagged Nef from this subcellular compartment. 2D gel analysis reveals the presence of Nef changes the content of lipid rafts and that Nef co-immunoprecipitates with several proteins in the raft fraction. The identity of these interactors obtained by peptide microsequencing should give insight into the molecular mechanism by which Nef induces a CD4 T cell transcriptional programme.

Published
2004
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46. Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila

Author

Matute, Juan D., Duan, Jinzhi, Flak, Magdalena B., Griebel, Paul, Tascon-Arcila, Jose A., Doms, Shauni, Hanley, Thomas, Antanaviciute, Agne, Gundrum, Jennifer, Mark Welch, Jessica L., Sit, Brandon, Abtahi, Shabnam, Fuhler, Gwenny M., Grootjans, Joep, Tran, Florian, Stengel, Stephanie T., White, James R., Krupka, Niklas, Haller, Dirk, Clare, Simon, Lawley, Trevor D., Kaser, Arthur, Simmons, Alison, Glickman, Jonathan N., Bry, Lynn, Rosenstiel, Philip, Borisy, Gary, Waldor, Matthew K., Baines, John F., Turner, Jerrold R., Blumberg, Richard S., Matute, Juan D [0000-0002-1703-8115], Duan, Jinzhi [0000-0001-9351-4956], Flak, Magdalena B [0000-0002-8238-9835], Griebel, Paul [0000-0001-5671-8183], Tascon-Arcila, Jose A [0000-0001-6647-2842], Doms, Shauni [0000-0002-2129-4138], Hanley, Thomas [0000-0002-4270-8299], Antanaviciute, Agne [0000-0002-9019-2215], Gundrum, Jennifer [0000-0001-8136-2537], Mark Welch, Jessica L [0000-0003-0696-2334], Sit, Brandon [0000-0003-2378-3039], Abtahi, Shabnam [0000-0003-3096-8023], Fuhler, Gwenny M [0000-0001-9221-4855], Grootjans, Joep [0000-0002-2805-4831], Tran, Florian [0000-0002-3735-9872], Stengel, Stephanie T [0000-0003-2949-879X], White, James R [0000-0002-7535-9179], Krupka, Niklas [0000-0001-5948-7536], Haller, Dirk [0000-0002-6977-4085], Clare, Simon [0000-0001-9368-6037], Lawley, Trevor D [0000-0002-4805-621X], Kaser, Arthur [0000-0003-1419-3344], Simmons, Alison [0000-0003-3454-0710], Glickman, Jonathan N [0000-0003-0910-2655], Bry, Lynn [0000-0002-8792-8527], Rosenstiel, Philip [0000-0002-9692-8828], Borisy, Gary [0000-0002-0266-8018], Waldor, Matthew K [0000-0003-1843-7000], Baines, John F [0000-0002-8132-4909], Turner, Jerrold R [0000-0003-0627-9455], Blumberg, Richard S [0000-0002-9704-248X], Apollo - University of Cambridge Repository, and Gastroenterology & Hepatology

Subjects
Mice, Mucus, Verrucomicrobia, Lectins, Humans, Animals, Colitis, Ulcerative
Abstract

Intelectin-1 (ITLN1) is a lectin secreted by intestinal epithelial cells (IECs) and upregulated in human ulcerative colitis (UC). We investigated how ITLN1 production is regulated in IECs and the biological effects of ITLN1 at the host-microbiota interface using mouse models. Our data show that ITLN1 upregulation in IECs from UC patients is a consequence of activating the unfolded protein response. Analysis of microbes coated by ITLN1 in vivo revealed a restricted subset of microorganisms, including the mucolytic bacterium Akkermansia muciniphila. Mice overexpressing intestinal ITLN1 exhibited decreased inner colonic mucus layer thickness and closer apposition of A. muciniphila to the epithelial cell surface, similar to alterations reported in UC. The changes in the inner mucus layer were microbiota and A. muciniphila dependent and associated with enhanced sensitivity to chemically induced and T cell-mediated colitis. We conclude that by determining the localization of a select group of bacteria to the mucus layer, ITLN1 modifies this critical barrier. Together, these findings may explain the impact of ITLN1 dysregulation on UC pathogenesis.

Published
2023

48. Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses

Author

Napolitani, Giorgio, Kurupati, Prathiba, Teng, Karen Wei Weng, Gibani, Malick M., Rei, Margarida, Aulicino, Anna, Preciado-Llanes, Lorena, Wong, Michael Thomas, Becht, Etienne, Howson, Lauren, de Haas, Paola, Salio, Mariolina, Blohmke, Christoph J., Olsen, Lars Rønn, Pinto, David Miguel Susano, Scifo, Laura, Jones, Claire, Dobinson, Hazel, Campbell, Danielle, Juel, Helene B., Thomaides-Brears, Helena, Pickard, Derek, Bumann, Dirk, Baker, Stephen, Dougan, Gordon, Simmons, Alison, Gordon, Melita A., Newell, Evan William, Pollard, Andrew J., and Cerundolo, Vincenzo

Published
2018
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