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2. A Shared Mission

Author

Kessler, Benedikt and Küppers, Almut

Subjects
Special aspects of education, LC8-6691, Drama, PN1600-3307
Abstract

Seit über zwanzig Jahren wird dem interkulturellen Lernen von Seiten der Pädagogik, der Fremdsprachendidaktik und vieler anderer Disziplinen große Aufmerksamkeit gewidmet. Die Theoriebildung ist weit ausdifferenziert; gleichzeitig ist zu konstatieren, dass manches Modell zur Implementierung der interkulturellen kommunikativen Kompetenzen (IKK) weit hinter seinen umfassenden theoretischen Ansprüchen zurückbleibt. Das Konzept der Interkulturellen Dramapädagogik stellt eine innovative methodische Antwort auf die Diskrepanz zwischen Anspruch und Wirklichkeit des interkulturellen Fremdsprachenunterrichts dar, indem es das Potenzial der Dramapädagogik für das interkulturelle Lernen und die Entwicklung der interkulturellen Handlungskompentenzen systematisch nutzt. Im folgenden Beitrag wird nach einer kurzen pädagogischen Standortbestimmung zunächst die Schnittstelle zwischen Dramapädagogik und interkultureller kommunikativer Kompetenz dargestellt. Es werden Zielsetzungen miteinander verglichen und Gemeinsamkeiten vorgestellt. In ihrer holistischen Ausrichtung weisen IKK und Dramapädagogik große Schnittmengen auf, die es für einen interkulturell ausgerichteten Fremdsprachenunterricht im Sinne einer Identitätsentwicklung zum intercultural speaker nutzbar zu machen gilt. Seit über zwanzig Jahren wird dem interkulturellen Lernen von Seiten der Pädagogik, der Fremdsprachendidaktik und vieler anderer Disziplinen große Aufmerksamkeit gewidmet. Die Theoriebildung ist weit ausdifferenziert; gleichzeitig ist zu konstatieren, dass manches Modell zur Implementierung der interkulturellen kommunikativen Kompetenzen (IKK) weit hinter seinen umfassenden theoretischen Ansprüchen zurückbleibt. Das Konzept der Interkulturellen Dramapädagogik stellt eine innovative methodische Antwort auf die Diskrepanz zwischen Anspruch und Wirklichkeit des interkulturellen Fremdsprachenunterrichts dar, indem es das Potenzial der Dramapädagogik für das interkulturelle Lernen und die Entwicklung der interkulturellen Handlungskompentenzen systematisch nutzt. Im folgenden Beitrag wird nach einer kurzen pädagogischen Standortbestimmung zunächst die Schnittstelle zwischen Dramapädagogik und interkultureller kommunikativer Kompetenz dargestellt. Es werden Zielsetzungen miteinander verglichen und Gemeinsamkeiten vorgestellt. In ihrer holistischen Ausrichtung weisen IKK und Dramapädagogik große Schnittmengen auf, die es für einen interkulturell ausgerichteten Fremdsprachenunterricht im Sinne einer Identitätsentwicklung zum intercultural speaker nutzbar zu machen gilt.

Published
2008
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3. A comprehensive analysis of the Bencao (herbal) small RNA Atlas reveals novel RNA therapeutics for treating human diseases

Author

Cao, Yinghao, Lin, Yexuan, Sun, Na, Du, Xinyi, Dong, Yixin, Mei, Song, Deng, Xingyu, Li, Xiaobei, Guo, Shaoting, Tang, Kegong, Liu, Jiaqi, Qiao, Xiangyu, Zhao, Dandan, Qin, Yuhao, Zhang, Cong, Xin, Tianyi, Shi, Xiaohu, Zhou, Congzhao, Dong, Tao, Guo, De-an, Kessler, Benedikt M., Xu, Dong, Song, Jingyuan, Huang, Fengming, Wang, Xiaoyue, and Jiang, Chengyu

Published
2023
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11. Type I interferon regulation by USP18 is a key vulnerability in cancer

Author

Jové, Veronica, Wheeler, Heather, Lee, Chiachin Wilson, Healy, David R., Levine, Kymberly, Ralph, Erik C., Yamaguchi, Masaya, Jiang, Ziyue Karen, Cabral, Edward, Xu, Yingrong, Stock, Jeffrey, Yang, Bing, Giddabasappa, Anand, Loria, Paula, Casimiro-Garcia, Agustin, Kessler, Benedikt M., Pinto-Fernández, Adán, Frattini, Véronique, Wes, Paul D., and Wang, Feng

Published
2024
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13. Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma

Author

Ahern, David, Amess, Bob, Ramirez, Kristen Aufiero, Berridge, Georgina, Carroll, Thomas M., Chadwick, Joseph A., Chang, Jaeho, Cheng, Jingfei, Dobbie, Sam T., Drozdz, Magdalena, Fischer, Roman, Frangou, Anna, Fuchs, Hannah S., Griffiths, Lucinda, Inoue, Masato, Jacobs, Brittany-Amber, James, Sabrina A., Kaplinsky, Joseph, Karydis, Ioannis, Kessler, Benedikt M., Lord, Simon R., Lou, Hantao, Lu, Xin, Macri, Mary J., McCann, Katy J., McGregor, Naomi, Middleton, Mark R., Norris-Bulpitt, Stewart, Omiyale, Ayo O., Owen, Richard P., Peneva, Iliana, Phetsouphanh, Chansavath, Rei, Margarida, Ricciardi, Toni, Roth, Andrew, Puig, Carlos Ruiz, Ryan, Aileen, Schuster-Böckler, Benjamin, Siejka-Zielińska, Paulina, Song, Chunxiao, Tomkova, Marketa, Van den Eynde, Benoit J., Velikova, Gergana, Venhaus, Ralph R., White, Michael J., and Xie, Phil F.

Published
2023
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18. Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity and inflammation due to dysregulated immunometabolism

Author

Cavounidis, Athena, Pandey, Sumeet, Capitani, Melania, Friedrich, Matthias, Cross, Amy, Gartner, Lisa, Aschenbrenner, Dominik, Kim-Schulze, Seunghee, Lam, Ying Ka, Berridge, Georgina, McGovern, Dermot P. B., Kessler, Benedikt, Fischer, Roman, Klenerman, Paul, Hester, Joanna, Issa, Fadi, Torres, Esther A., Powrie, Fiona, Gochuico, Bernadette R., Gahl, William A., Cohen, Louis, and Uhlig, Holm H.

Published
2022
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21. Drosophila Sex Peptide controls the assembly of lipid microcarriers in seminal fluid

Author

Wainwright, S. Mark, Hopkins, Ben R., Mendes, Cláudia C., Sekar, Aashika, Kroeger, Benjamin, Hellberg, Josephine E. E. U., Fan, Shih-Jung, Pavey, Abigail, Marie, Pauline P., Leiblich, Aaron, Sepil, Irem, Charles, Philip D., Thézénas, Marie L., Fischer, Roman, Kessler, Benedikt M., Gandy, Carina, Corrigan, Laura, Patel, Rachel, Wigby, Stuart, Morris, John F., Goberdhan, Deborah C. I., and Wilson, Clive

Published
2021

27. Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates

Author

Keating, Sheila M, Heitman, John W, Wu, Shiquan, Deng, Xutao, Stacey, Andrea R, Zahn, Roland C, de la Rosa, Maurus, Finstad, Samantha L, Lifson, Jeffrey D, Piatak, Michael, Gauduin, Marie-Claire, Kessler, Benedikt M, Ternette, Nicola, Carville, Angela, Johnson, R Paul, Desrosiers, Ronald C, Letvin, Norman L, Borrow, Persephone, Norris, Philip J, and Schmitz, Joern E

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Vaccine Related, Infectious Diseases, Inflammatory and immune system, Infection, Good Health and Well Being, Acute Disease, Animals, Chemokines, Cytokines, HIV, HIV Infections, Humans, Inflammation, Leukocytes, Mononuclear, Primates, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, Viremia, Simian immunodeficiency virus, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Acute human immunodeficiency virus (HIV) infection represents a period of intense immune perturbation and activation of the host immune system. Study of the eclipse and viral expansion phases of infection is difficult in humans, but studies in nonprogressive and progressive nonhuman primate (NHP) infection models can provide significant insight into critical events occurring during this time. Cytokines, chemokines, and other soluble immune factors were measured in longitudinal samples from rhesus macaques infected with either SIVmac251 (progressive infection) or SIVmac239Δnef (attenuated/nonprogressive infection) and from African green monkeys infected with SIVsab9315BR (nonpathogenic infection). Levels of acute-phase peak viral replication were highest in SIVmac251 infection but correlated positively with viremia at 3 months postinfection in all three infection models. SIVmac251 infection was associated with stronger corresponding acute-phase cytokine/chemokine responses than the nonprogressive infections. The production of interleukin 15 (IL-15), IL-18, gamma interferon (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1β (MIP-1β), and serum amyloid A protein (SAA) during acute SIVmac251 infection, but not during SIVmac239Δnef or SIVsab9315BR infection, correlated positively with chronic viremia at 3 months postinfection. Acute-phase production of MCP-1 correlated with viremia at 3 months postinfection in both nonprogressive infections. Finally, a positive correlation between the acute-phase area under the curve (AUC) for IL-6 and soluble CD40 ligand (sCD40L) and chronic viremia was observed only for the nonprogressive infection models. While we observed dynamic acute inflammatory immune responses in both progressive and nonprogressive SIV infections, the responses in the nonprogressive infections were not only lower in magnitude but also qualitatively different biomarkers of disease progression.ImportanceNHP models of HIV infection constitute a powerful tool with which to study viral pathogenesis in order to gain critical information for a better understanding of HIV infection in humans. Here we studied progressive and nonprogressive simian immunodeficiency virus (SIV) infection models in both natural and nonnatural host NHP species. Regardless of the pathogenicity of the virus infection and regardless of the NHP species studied, the magnitude of viremia, as measured by area under the curve, during the first 4 weeks of infection correlated positively with viremia in chronic infection. The magnitude of cytokine and chemokine responses during primary infection also correlated positively with both acute-phase and chronic viremia. However, the pattern and levels of specific cytokines and chemokines produced differed between nonprogressive and progressive SIV infection models. The qualitative differences in the early immune response in pathogenic and nonpathogenic infections identified here may be important determinants of the subsequent disease course.

Published
2016

28. Identification of high-performing antibodies for the reliable detection of Tau proteoforms by Western blotting and immunohistochemistry

Author

Ellis, Michael J., Lekka, Christiana, Holden, Katie L., Tulmin, Hanna, Seedat, Faheem, O’Brien, Darragh P., Dhayal, Shalinee, Zeissler, Marie Louise, Knudsen, Jakob G., Kessler, Benedikt M., Morgan, Noel G., Todd, John A., Richardson, Sarah J., Stefana, M. Irina, Ellis, Michael J., Lekka, Christiana, Holden, Katie L., Tulmin, Hanna, Seedat, Faheem, O’Brien, Darragh P., Dhayal, Shalinee, Zeissler, Marie Louise, Knudsen, Jakob G., Kessler, Benedikt M., Morgan, Noel G., Todd, John A., Richardson, Sarah J., and Stefana, M. Irina

Abstract

Antibodies are essential research tools whose performance directly impacts research conclusions and reproducibility. Owing to its central role in Alzheimer’s disease and other dementias, hundreds of distinct antibody clones have been developed against the microtubule-associated protein Tau and its multiple proteoforms. Despite this breadth of offer, limited understanding of their performance and poor antibody selectivity have hindered research progress. Here, we validate a large panel of Tau antibodies by Western blot (79 reagents) and immunohistochemistry (35 reagents). We address the reagents’ ability to detect the target proteoform, selectivity, the impact of protein phosphorylation on antibody binding and performance in human brain samples. While most antibodies detected Tau at high levels, many failed to detect it at lower, endogenous levels. By WB, non-selective binding to other proteins affected over half of the antibodies tested, with several cross-reacting with the related MAP2 protein, whereas the “oligomeric Tau” T22 antibody reacted with monomeric Tau by WB, thus calling into question its specificity to Tau oligomers. Despite the presumption that “total” Tau antibodies are agnostic to post-translational modifications, we found that phosphorylation partially inhibits binding for many such antibodies, including the popular Tau-5 clone. We further combine high-sensitivity reagents, mass-spectrometry proteomics and cDNA sequencing to demonstrate that presumptive Tau “knockout” human cells continue to express residual protein arising through exon skipping, providing evidence of previously unappreciated gene plasticity. Finally, probing of human brain samples with a large panel of antibodies revealed the presence of C-term-truncated versions of all main Tau brain isoforms in both control and tauopathy donors. Ultimately, we identify a validated panel of Tau antibodies that can be employed in Western blotting and/or immunohistochemistry to reliably detect even, Antibodies are essential research tools whose performance directly impacts research conclusions and reproducibility. Owing to its central role in Alzheimer’s disease and other dementias, hundreds of distinct antibody clones have been developed against the microtubule-associated protein Tau and its multiple proteoforms. Despite this breadth of offer, limited understanding of their performance and poor antibody selectivity have hindered research progress. Here, we validate a large panel of Tau antibodies by Western blot (79 reagents) and immunohistochemistry (35 reagents). We address the reagents’ ability to detect the target proteoform, selectivity, the impact of protein phosphorylation on antibody binding and performance in human brain samples. While most antibodies detected Tau at high levels, many failed to detect it at lower, endogenous levels. By WB, non-selective binding to other proteins affected over half of the antibodies tested, with several cross-reacting with the related MAP2 protein, whereas the “oligomeric Tau” T22 antibody reacted with monomeric Tau by WB, thus calling into question its specificity to Tau oligomers. Despite the presumption that “total” Tau antibodies are agnostic to post-translational modifications, we found that phosphorylation partially inhibits binding for many such antibodies, including the popular Tau-5 clone. We further combine high-sensitivity reagents, mass-spectrometry proteomics and cDNA sequencing to demonstrate that presumptive Tau “knockout” human cells continue to express residual protein arising through exon skipping, providing evidence of previously unappreciated gene plasticity. Finally, probing of human brain samples with a large panel of antibodies revealed the presence of C-term-truncated versions of all main Tau brain isoforms in both control and tauopathy donors. Ultimately, we identify a validated panel of Tau antibodies that can be employed in Western blotting and/or immunohistochemistry to reliably detect ev

Published
2024

29. Oncogenic mutations of KRAS modulate its turnover by the CUL3/LZTR1 E3 ligase complex

Author

Damianou, Andreas, Liang, Zhu, Lassen, Frederik, Vendrell, Iolanda, Vere, George, Hester, Svenja, Charles, Philip D., Pinto-Fernandez, Adan, Santos, Alberto, Fischer, Roman, Kessler, Benedikt M., Damianou, Andreas, Liang, Zhu, Lassen, Frederik, Vendrell, Iolanda, Vere, George, Hester, Svenja, Charles, Philip D., Pinto-Fernandez, Adan, Santos, Alberto, Fischer, Roman, and Kessler, Benedikt M.

Abstract

KRAS is a proto-oncogene encoding a small GTPase. Mutations contribute to ~30% of human solid tumours, including lung adenocarcinoma, pancreatic, and colorectal carcinomas. Most KRAS activating mutations interfere with GTP hydrolysis, essential for its role as a molecular switch, leading to alterations in their molecular environment and oncogenic signalling. However, the precise signalling cascades these mutations affect are poorly understood. Here, APEX2 proximity labelling was used to profile the molecular environment of WT, G12D, G13D, and Q61Hactivating KRAS mutants under starvation and stimulation conditions. Through quantitative proteomics, we demonstrate the presence of known KRAS interactors, including ARAF and LZTR1, which are differentially captured by WT and KRAS mutants. Notably, the KRAS mutations G12D, G13D, and Q61H abrogate their association with LZTR1, thereby affecting turnover. Elucidating the implications of LZTR1-mediated regulation of KRAS protein levels in cancer may offer insights into therapeutic strategies targeting KRAS-driven malignancies.

Published
2024

31. Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity

Author

Pinto-Fernandez, Adan, Salio, Mariolina, Partridge, Tom, Chen, Jianzhou, Vere, George, Greenwood, Helene, Olie, Cyriel Sebastiaan, Damianou, Andreas, Scott, Hannah Claire, Pegg, Henry Jack, Chiarenza, Alessandra, Díaz-Saez, Laura, Smith, Paul, Gonzalez-Lopez, Claudia, Patel, Bhavisha, Anderton, Emma, Jones, Neil, Hammonds, Tim R., Huber, Kilian, Muschel, Ruth, Borrow, Persephone, Cerundolo, Vincenzo, and Kessler, Benedikt M.

Published
2021
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32. Association of Indoleamine 2,3-Dioxygenase (IDO) Activity with Outcome after Cardiac Surgery in Adult Patients.

Author

Stieger, Andrea, Huber, Markus, Yu, Zhanru, Kessler, Benedikt M., Fischer, Roman, Andereggen, Lukas, Kobel, Beatrice, Stueber, Frank, Luedi, Markus M., and Filipovic, Mark G.

Subjects
INDOLEAMINE 2,3-dioxygenase, CARDIAC surgery, CARDIOPULMONARY bypass, TREATMENT effectiveness, SURGICAL complications, DIOXYGENASES
Abstract

Indoleamine 2,3-deoxygenase (IDO) plays an important role in the catabolism of the amino acid tryptophan. Tryptophan and its metabolites are key immune modulators. Increased IDO activity has been observed in various diseases and is associated with worse clinical outcomes. However, comprehensive research regarding its role in cardiac surgery remains limited. Therefore, we aimed to investigate perioperative changes in IDO activity and pathway metabolites, along with their impact on clinical outcomes in adult patients undergoing cardiac surgery. As an observational cohort study conducted at the Inselspital in Bern from January to December 2019, we retrospectively analyzed the data of prospectively collected biobank samples of patients undergoing cardiac surgery with the use of cardiopulmonary bypass. IDO pathway metabolite analysis was conducted by mass spectrometry. Perioperative dynamics were descriptively assessed and associated with pre-defined clinical outcome measures (30-day mortality, 1-year mortality, incidence of stroke and myocardial infarction, and length of hospital stay) through a multi-step exploratory regression analysis. A cohort of 192 adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass were included (median age 67.0, IQR 60.0–73.0, 75.5% male). A significant perioperative decrease in the kynurenine/tryptophan (Kyn/Trp) ratio (−2.298, 95% CI −4.028 to −596, p = 0.009) and significant perioperative dynamics in the associated metabolites was observed. No association of perioperative changes in IDO activity and pathway metabolites with clinical outcomes was found. A significant decrease in the Kyn/Trp ratio among adult patients undergoing cardiac surgery indicates a perioperative downregulation of IDO, which stands in contrast to other pro-inflammatory conditions. Further studies are needed to investigate IDO in the setting of perioperative immunomodulation, which is a key driver of postoperative complications in cardiac surgery patients. [ABSTRACT FROM AUTHOR]

Published
2024
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35. USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism

Author

Gan, Jin, primary, Pinto-Fernández, Adán, additional, Flierman, Dennis, additional, Akkermans, Jimmy J. L. L., additional, O’Brien, Darragh P., additional, Greenwood, Helene, additional, Scott, Hannah Claire, additional, Fritz, Günter, additional, Knobeloch, Klaus-Peter, additional, Neefjes, Jacques, additional, van Dam, Hans, additional, Ovaa, Huib, additional, Ploegh, Hidde L., additional, Kessler, Benedikt M., additional, Geurink, Paul P., additional, and Sapmaz, Aysegul, additional

Published
2023
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37. Molecular insights into an ancient form of Paget’s disease of bone

Author

Shaw, Barry, Burrell, Carla L., Green, Darrell, Navarro-Martinez, Ana, Scott, Daniel, Daroszewska, Anna, van ’t Hof, Rob, Smith, Lynn, Hargrave, Frank, Mistry, Sharad, Bottrill, Andrew, Kessler, Benedikt M., Fischer, Roman, Singh, Archana, Dalmay, Tamas, Fraser, William D., Henneberger, Kirstin, King, Turi, Gonzalez, Silvia, and Layfield, Robert

Published
2019

47. Structural Premise of Selective Deubiquitinase USP30 Inhibition by Small-Molecule Benzosulfonamides

Author

O'Brien, Darragh P., primary, Jones, Hannah B.L., additional, Guenther, Franziska, additional, Murphy, Emma J., additional, England, Katherine S., additional, Vendrell, Iolanda, additional, Anderson, Malcolm, additional, Brennan, Paul E., additional, Davis, John B., additional, Pinto-Fernández, Adán, additional, Turnbull, Andrew P., additional, and Kessler, Benedikt M., additional

Published
2023
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48. 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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