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3. Compaction and cementation controls on reservoir quality in Buntsandstein red beds

Author

Schmidt, Christina

Subjects
Diagenese, Bleichung, Reservoirqualität, triassische Sandsteine, laterale Variabilität, diagenesis, bleaching, reservoir quality, Triassic red beds, lateral variability, bic Book Industry Communication::R Earth sciences, geography, environment, planning
Abstract

Reservoir quality in fluvial siliciclastic rocks is variable. Permeability is influenced by micron-scale grain coatings or bedding style on the m-/km-scale. Outcrops allow the analysis of depositional environments and diagenesis, thus an investigation of reservoir quality controls. A process-oriented approach is used to understand variability in a meander deposit, compaction and cementation behavior of lithofacies types during burial and the discrepancy between porosity and permeability values.

Published
2022
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6. SARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds

Author

Reinke, Patrick Y. A., Schubert, Robin, Oberthür, Dominik, Galchenkova, Marina, Rahmani Mashhour, Aida, Günther, Sebastian, Chretien, Anaïs, Round, Adam, Seychell, Brandon Charles, Norton-Baker, Brenna, Kim, Chan, Schmidt, Christina, Koua, Faisal H. M., Tolstikova, Alexandra, Ewert, Wiebke, Peña Murillo, Gisel Esperanza, Mills, Grant, Kirkwood, Henry, Brognaro, Hévila, Han, Huijong, Koliyadu, Jayanath, Schulz, Joachim, Bielecki, Johan, Lieske, Julia, Maracke, Julia, Knoska, Juraj, Lorenzen, Kristina, Brings, Lea, Sikorski, Marcin, Kloos, Marco, Vakili, Mohammad, Vagovic, Patrik, Middendorf, Philipp, de Wijn, Raphael, Bean, Richard, Letrun, Romain, Han, Seonghyun, Falke, Sven, Geng, Tian, Sato, Tokushi, Srinivasan, Vasundara, Kim, Yoonhee, Yefanov, Oleksandr M., Gelisio, Luca, Beck, Tobias, Doré, Andrew S., Mancuso, Adrian P., Betzel, Christian, Bajt, Saša, Redecke, Lars, Chapman, Henry N., Meents, Alke, Turk, Dušan, Hinrichs, Winfried, and Lane, Thomas J.

Published
2024
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7. Author Correction: In vivo marker of brainstem myelin is associated to quantitative sleep parameters in healthy young men

Author

Talwar, Puneet, Deantoni, Michele, Van Egroo, Maxime, Muto, Vincenzo, Chylinski, Daphne, Koshmanova, Ekaterina, Jaspar, Mathieu, Meyer, Christelle, Degueldre, Christian, Berthomier, Christian, Luxen, André, Salmon, Eric, Collette, Fabienne, Dijk, D.-J., Schmidt, Christina, Phillips, Christophe, Maquet, Pierre, Sherif, Siya, and Vandewalle, Gilles

Published
2024
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8. Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes

Author

Moschandrea, Chrysanthi, Kondylis, Vangelis, Evangelakos, Ioannis, Herholz, Marija, Schneider, Farina, Schmidt, Christina, Yang, Ming, Ehret, Sandra, Heine, Markus, Jaeckstein, Michelle Y., Szczepanowska, Karolina, Schwarzer, Robin, Baumann, Linda, Bock, Theresa, Nikitopoulou, Efterpi, Brodesser, Susanne, Krüger, Marcus, Frezza, Christian, Heeren, Joerg, Trifunovic, Aleksandra, and Pasparakis, Manolis

Published
2024
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9. Care across the gender spectrum: A transgender health curriculum in the Obstetrics and Gynecology clerkship.

Author

Schmidt, Christina, Stretten, Monica, Bindman, Jay, Pettigrew, Gaetan, and Lager, Jeannette

Subjects
Gender diverse, Gender-affirming care, Transgender, Undergraduate medical education, Clinical Clerkship, Curriculum, Gynecology, Humans, Obstetrics, Students, Medical, Transgender Persons
Abstract

BACKGROUND: A lack of undergraduate medical curricula on providing healthcare to transgender and gender diverse (TGD) patients has contributed to significant health disparities for TGD communities. To address this gap, we designed and evaluated a novel curriculum to train Obstetrics and Gynecology (OB/GYN) clerkship students in caring for TGD patients. METHODS: Following Kerns 6-step method for curriculum development, we created a two-part curriculum on TGD healthcare topics - an online module on gender-affirming care, followed by a series of interactive cases on TGD-specific health topics. Undergraduate medical students completing their core OB/GYN clerkships at a university academic medical center (January-December 2021) were invited to complete this curriculum. Participants completed pre/post assessment surveys to assess their experience caring for TGD patients, as well as a scored knowledge assessment before and after completing the curriculum. RESULTS: Sixty-five students participated in this curricular assessment. Prior to completing the module, 45% agreed that they had received adequate TGD health training. Following module completion, students reported increased comfort in caring for transgender patients (49.2% vs. 81.5%; p

Published
2022

11. Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease

Author

Jones, Richard E., Gruszczyk, Anja V., Schmidt, Christina, Hammersley, Daniel J., Mach, Lukas, Lee, Michael, Wong, Joyce, Yang, Ming, Hatipoglu, Suzan, Lota, Amrit S., Barnett, Sam N., Toscano-Rivalta, Rebecca, Owen, Ruth, Raja, Shahzad, De Robertis, Fabio, Smail, Hassiba, De-Souza, Anthony, Stock, Ulrich, Kellman, Peter, Griffin, Julian, Dumas, Marc-Emmanuel, Martin, Jack L., Saeb-Parsy, Kourosh, Vazir, Ali, Cleland, John G. F., Pennell, Dudley J., Bhudia, Sunil K., Halliday, Brian P., Noseda, Michela, Frezza, Christian, Murphy, Michael P., and Prasad, Sanjay K.

Published
2023
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12. The ribosomal protein S6 kinase alpha-1 (RPS6KA1) induces resistance to venetoclax/azacitidine in acute myeloid leukemia

Author

Weidenauer, Katharina, Schmidt, Christina, Rohde, Christian, Pauli, Cornelius, Blank, Maximilian F., Heid, Daniel, Waclawiczek, Alexander, Corbacioglu, Anika, Göllner, Stefanie, Lotze, Michelle, Vierbaum, Lisa, Renders, Simon, Krijgsveld, Jeroen, Raffel, Simon, Sauer, Tim, Trumpp, Andreas, Pabst, Caroline, Müller-Tidow, Carsten, and Janssen, Maike

Published
2023
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13. Trends and outcomes for deliveries with hypertensive disorders of pregnancy from 2000 to 2018: A repeated cross‐sectional study

Author

Wen, Timothy, Schmidt, Christina N, Sobhani, Nasim C, Guglielminotti, Jean, Miller, Eliza C, Sutton, Desmond, Lahtermaher, Yael, D’Alton, Mary E, and Friedman, Alexander M

Subjects
Liver Disease, Digestive Diseases, Kidney Disease, Brain Disorders, Prevention, Stroke, Reproductive health and childbirth, Good Health and Well Being, Acute Kidney Injury, Cross-Sectional Studies, Female, Humans, Hypertension, Pregnancy-Induced, Pre-Eclampsia, Pregnancy, Prevalence, hypertensive disorders of pregnancy, maternal safety, pre-eclampsia, severe maternal morbidity, Medical and Health Sciences, Obstetrics & Reproductive Medicine
Abstract

ObjectiveTo analyse trends, risk factors, and outcomes related to hypertensive disorders of pregnancy (HDP).DesignRepeated cross-sectional.SettingUS delivery hospitalisations.PopulationDelivery hospitalisations in the 2000-2018 National Inpatient Sample.MethodsUS hospital delivery hospitalisations with HDP were analysed. Several trends were analysed: (i) the proportion of deliveries by year with HDP, (ii) the proportion of deliveries with HDP risk factors and (iii) adverse outcomes associated with HDP including maternal stroke, acute renal failure and acute liver injury. Risk ratios were determined using regression models with HDP as the exposure of interest.Main outcome measuresPrevalence of HDP, risk factors for HDP and associated adverse outcomes.ResultsOf 73.1 million delivery hospitalisations, 7.7% had an associated diagnosis of HDP. Over the study period, HDP doubled from 6.0% of deliveries in 2000 to 12.0% in 2018. The proportion of deliveries with risk factors for HDP increased from 9.6% in 2000 to 24.6% in 2018. In adjusted models, HDP were associated with increased stroke (aRR [adjusted risk ratio] 15.9, 95% CI 14.8-17.1), acute renal failure (aRR 13.8, 95% CI 13.5-14.2) and acute liver injury (aRR 1.2, 95% CI 1.2-1.3). Among deliveries with HDP, acute renal failure and acute liver injury increased; in comparison, stroke decreased.ConclusionHypertensive disorders of pregnancy increased in the setting of risk factors for HDP becoming more common, whereas stroke decreased.Tweetable abstractWhile hypertensive disorders of pregnancy increased from 2000 to 2018, stroke appears to be decreasing.

Published
2022

14. In vivo marker of brainstem myelin is associated to quantitative sleep parameters in healthy young men

Author

Talwar, Puneet, Deantoni, Michele, Van Egroo, Maxime, Muto, Vincenzo, Chylinski, Daphne, Koshmanova, Ekaterina, Jaspar, Mathieu, Meyer, Christelle, Degueldre, Christian, Berthomier, Christian, Luxen, André, Salmon, Eric, Collette, Fabienne, Dijk, D.-J., Schmidt, Christina, Phillips, Christophe, Maquet, Pierre, Sherif, Siya, and Vandewalle, Gilles

Published
2023
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16. Light-induced Trpin/Metout Switching During BLUF Domain Activation in ATP-bound Photoactivatable Adenylate Cyclase OaPAC

Author

Chretien, Anaïs, Nagel, Marius F., Botha, Sabine, de Wijn, Raphaël, Brings, Lea, Dörner, Katerina, Han, Huijong, Koliyadu, Jayanath C.P., Letrun, Romain, Round, Adam, Sato, Tokushi, Schmidt, Christina, Secareanu, Radu-Costin, von Stetten, David, Vakili, Mohammad, Wrona, Agnieszka, Bean, Richard, Mancuso, Adrian, Schulz, Joachim, Pearson, Arwen R., Kottke, Tilman, Lorenzen, Kristina, and Schubert, Robin

Published
2024
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20. The generation of a human cell line to elucidate the role of Fumarate Hydratase loss in cancer

Author

Schmidt, Christina and Frezza, Christian

Subjects
Mitochondria, Cancer Metabolism, Fumarate Hydratase
Abstract

The reprogramming of cellular metabolism is an established hallmark of cancer, which enables cancer cells to survive, proliferate, and metastasize even under harsh environmental conditions. These cancer-associated metabolic changes can affect several pathways one of which is mitochondrial metabolism. The suppression of mitochondrial metabolism has been associated with poor clinical outcomes and mitochondrial dysfunction has been associated with some hereditary and sporadic forms of cancer that arise from mutations in mitochondrial genes. Understanding the mechanisms responsible for cellular transformation and subsequent tumour formation in these hereditary, metabolically-impaired tumours could link dysregulated mitochondrial function and tumour formation. Hereditary mutations and subsequent loss of the mitochondrial TCA cycle enzyme fumarate hydratase (FH) leads to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), an aggressive form of renal cancer associated with poor clinical outcome. The loss of FH triggers the accumulation of fumarate, which induces a multi-layer cellular reprogramming that contributes to tumorigenesis. Yet, it is unclear how FH loss influences the whole gene expression landscape and if the gene expression is regulated on the level of DNA-methylation, transcription or translation. In this thesis, I generated the first FH-deficient human renal epithelial cell lines using CRISPR/Cas9-based genome editing, and applied proteomics, metabolomics, and transcriptomics approaches to investigate how the loss of FH alters these cellular layers. First, I confirmed that this model faithfully recapitulates the biochemical and phenotypic markers of FH-deficiency as previously reported. Next, I developed a novel multi-omics tool, SiRCle (Signature Regulatory Clusters) to disentangle this interconnected network of signalling cascades. Using SiRCle, I extracted clusters of increased/decreased gene expression that are regulated at the level of DNA methylation, transcription, and/or translation, and identified which clusters drive which phenotype of FH loss. By mapping the transcription factors that drive the genes of each cluster, I identified unique drivers that could be responsible for the cellular rewiring after FH loss. It is now clear that the tumour microenvironment affects the phenotype of cancer cells, and hence that metabolic rewiring becomes essential for tumour cells to strive even under harsh environmental conditions. Yet, its effect on FH-deficient cells’ behaviour is currently unknown. In this part of the thesis, I used a Tumour Roll for Analysis of Cellular Environment and Response (TRACER), a 3D scaffold that develops oxygen and nutrient gradients similar to those observed in tumours. Using TRACER, I show that the main metabolic signature of FH loss, which is driven by the high levels of fumarate, is not influenced by the nutrient and oxygen gradients generated in this 3D model. Consequently, FH loss is a stronger driver of the metabolic signature than environmental cues. Moreover, by applying linear modelling to the metabolic profile of the cells over the different layers, I identify specific layer-dependent metabolic signatures in FH-deficient cells that are not observed in 2D culture. These results imply that in vivo FH loss could undergo previously unacknowledged compensatory metabolic changes, which underlines the important role of the microenvironment in dictating the phenotype of cancer cells.

Published
2021
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23. FOXA2 controls the anti-oxidant response in FH-deficient cells

Author

Rogerson, Connor, Sciacovelli, Marco, Maddalena, Lucas A., Pouikli, Andromachi, Segarra-Mondejar, Marc, Valcarcel-Jimenez, Lorea, Schmidt, Christina, Yang, Ming, Ivanova, Elena, Kent, Joshua, Mora, Ariane, Cheeseman, Danya, Carroll, Jason S., Kelsey, Gavin, and Frezza, Christian

Published
2023
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25. Association between sleep slow-wave activity and in-vivo estimates of myelin in healthy young men

Author

Deantoni, Michele, Baillet, Marion, Hammad, Gregory, Berthomier, Christian, Reyt, Mathilde, Jaspar, Mathieu, Meyer, Christelle, Van Egroo, Maxime, Talwar, Puneet, Lambot, Eric, Chellappa, Sarah L., Degueldre, Christian, Luxen, André, Salmon, Eric, Balteau, Evelyne, Phillips, Christophe, Dijk, Derk-Jan, Vandewalle, Gilles, Collette, Fabienne, Maquet, Pierre, Muto, Vincenzo, and Schmidt, Christina

Published
2023
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29. Minimized Sample Consumption for Time-Resolved Serial Crystallography Applied to the Redox Cycle of Human NQO1

Author

Doppler, Diandra, primary, Grieco, Alice, additional, Koh, Domin, additional, Manna, Abhik, additional, Ansari, Adil, additional, Alvarez, Roberto, additional, Karpos, Konstantinos, additional, Le, Hung, additional, Sonker, Mukul, additional, Ketawala, Gihan, additional, Mahmud, Samira, additional, Quereda Moraleda, Isabel, additional, Pey, Angel Luis, additional, Letrun, Roman, additional, Doerner, Katerina, additional, Koliyadu, Jayanath C. P., additional, de Wijn, Raphael, additional, Bielecki, Johan, additional, Han, Huijong, additional, Kim, Chan, additional, Koua, Faisal, additional, Round, Adam, additional, Sarma, Abhisakh, additional, Sato, Tokushi, additional, Schmidt, Christina, additional, Vakili, Mohammad, additional, Zabelskii, Dmitrii, additional, Bean, Richard, additional, Mancuso, Adrian P., additional, Schulz, Joachim, additional, Fromme, Raimund, additional, Medina, Milagros, additional, Grant, Thomas D, additional, Fromme, Petra, additional, Kirian, Richard A., additional, Botha, Sabine, additional, Martin Garcia, Jose Manuel, additional, and Ros, Alexandra, additional

Published
2024
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30. Venetoclax synergizes with gilteritinib in FLT3 wild-type high-risk acute myeloid leukemia by suppressing MCL-1

Author

Janssen, Maike, Schmidt, Christina, Bruch, Peter-Martin, Blank, Maximilian F., Rohde, Christian, Waclawiczek, Alexander, Heid, Daniel, Renders, Simon, Göllner, Stefanie, Vierbaum, Lisa, Besenbeck, Birgit, Herbst, Sophie A., Knoll, Mareike, Kolb, Carolin, Przybylla, Adriana, Weidenauer, Katharina, Ludwig, Anne Kathrin, Fabre, Margarete, Gu, Muxin, Schlenk, Richard F., Stölzel, Friedrich, Bornhäuser, Martin, Röllig, Christoph, Platzbecker, Uwe, Baldus, Claudia, Serve, Hubert, Sauer, Tim, Raffel, Simon, Pabst, Caroline, Vassiliou, George, Vick, Binje, Jeremias, Irmela, Trumpp, Andreas, Krijgsveld, Jeroen, Müller-Tidow, Carsten, and Dietrich, Sascha

Published
2022
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32. Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease

Author

Srinivasan, Vasundara, Brognaro, Hévila, Prabhu, Prince R., de Souza, Edmarcia Elisa, Günther, Sebastian, Reinke, Patrick Y. A., Lane, Thomas J., Ginn, Helen, Han, Huijong, Ewert, Wiebke, Sprenger, Janina, Koua, Faisal H. M., Falke, Sven, Werner, Nadine, Andaleeb, Hina, Ullah, Najeeb, Franca, Bruno Alves, Wang, Mengying, Barra, Angélica Luana C., Perbandt, Markus, Schwinzer, Martin, Schmidt, Christina, Brings, Lea, Lorenzen, Kristina, Schubert, Robin, Machado, Rafael Rahal Guaragna, Candido, Erika Donizette, Oliveira, Danielle Bruna Leal, Durigon, Edison Luiz, Niebling, Stephan, Garcia, Angelica Struve, Yefanov, Oleksandr, Lieske, Julia, Gelisio, Luca, Domaracky, Martin, Middendorf, Philipp, Groessler, Michael, Trost, Fabian, Galchenkova, Marina, Mashhour, Aida Rahmani, Saouane, Sofiane, Hakanpää, Johanna, Wolf, Markus, Alai, Maria Garcia, Turk, Dusan, Pearson, Arwen R., Chapman, Henry N., Hinrichs, Winfried, Wrenger, Carsten, Meents, Alke, and Betzel, Christian

Published
2022
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33. Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression

Author

Sciacovelli, Marco, Dugourd, Aurelien, Jimenez, Lorea Valcarcel, Yang, Ming, Nikitopoulou, Efterpi, Costa, Ana S. H., Tronci, Laura, Caraffini, Veronica, Rodrigues, Paulo, Schmidt, Christina, Ryan, Dylan Gerard, Young, Timothy, Zecchini, Vincent R., Rossi, Sabrina H., Massie, Charlie, Lohoff, Caroline, Masid, Maria, Hatzimanikatis, Vassily, Kuppe, Christoph, Von Kriegsheim, Alex, Kramann, Rafael, Gnanapragasam, Vincent, Warren, Anne Y., Stewart, Grant D., Erez, Ayelet, Vanharanta, Sakari, Saez-Rodriguez, Julio, and Frezza, Christian

Published
2022
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35. "Den løse ramme var svær" -- en gentænkning af forandring, samarbejde og bevægelse i intra-aktiv aktionsforskning.

Author

Schmidt, Christina Haandbæk and Kortbek, Hjørdis Brandrup

Abstract

"The Loose Framework was Challenging": A Reconsideration of Change, Collaboration, and Movement in Intra-Active Action Research The purpose of this article is to contribute to the discussion on how action research can create change and establish equitable relationships between practice and research. In the article, we engage in a dialogue regarding what can be understood as intra-active action research and argue that in its endeavor to incorporate a perspective on materiality, action research tends to overlook the significance of discourses in shaping relationships. In line with this, we explore how the potentially contradictory demands of action research for change as both emancipation and utility can be understood as discourses that are linked to knowledge production and materialise in relationships. Consequently, there is a need to rethink the relationship between discourses, materiality, and subjects in intra-active action research. The article engages in a dialogue with Moa Frid's (2021) article "Collaboration, movement, and change: An intraactive action research approach" and seeks to reframe Frid's reconsideration with a heighten ed focus on the significance of discourses. Our reconsideration is exemplified through empirical material from a research project. [ABSTRACT FROM AUTHOR]

Published
2024
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36. MetalinksDB: a flexible and contextualizable resource of metabolite-protein interactions.

Author

Farr, Elias, Dimitrov, Daniel, Schmidt, Christina, Turei, Denes, Lobentanzer, Sebastian, Dugourd, Aurelien, and Saez-Rodriguez, Julio

Subjects
KNOWLEDGE graphs, ACUTE kidney failure, CELL communication, CELL receptors, TRANSCRIPTOMES
Abstract

From the catalytic breakdown of nutrients to signaling, interactions between metabolites and proteins play an essential role in cellular function. An important case is cell–cell communication, where metabolites, secreted into the microenvironment, initiate signaling cascades by binding to intra- or extracellular receptors of neighboring cells. Protein–protein cell–cell communication interactions are routinely predicted from transcriptomic data. However, inferring metabolite-mediated intercellular signaling remains challenging, partially due to the limited size of intercellular prior knowledge resources focused on metabolites. Here, we leverage knowledge-graph infrastructure to integrate generalistic metabolite-protein with curated metabolite-receptor resources to create MetalinksDB. MetalinksDB is an order of magnitude larger than existing metabolite-receptor resources and can be tailored to specific biological contexts, such as diseases, pathways, or tissue/cellular locations. We demonstrate MetalinksDB's utility in identifying deregulated processes in renal cancer using multi-omics bulk data. Furthermore, we infer metabolite-driven intercellular signaling in acute kidney injury using spatial transcriptomics data. MetalinksDB is a comprehensive and customizable database of intercellular metabolite-protein interactions, accessible via a web interface (https://metalinks.omnipathdb.org/) and programmatically as a knowledge graph (https://github.com/biocypher/metalinks). We anticipate that by enabling diverse analyses tailored to specific biological contexts, MetalinksDB will facilitate the discovery of disease-relevant metabolite-mediated intercellular signaling processes. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas

Author

Hübschmann, Daniel, Kleinheinz, Kortine, Wagener, Rabea, Bernhart, Stephan H., López, Cristina, Toprak, Umut H., Sungalee, Stephanie, Ishaque, Naveed, Kretzmer, Helene, Kreuz, Markus, Waszak, Sebastian M., Paramasivam, Nagarajan, Ammerpohl, Ole, Aukema, Sietse M., Beekman, Renée, Bergmann, Anke K., Bieg, Matthias, Binder, Hans, Borkhardt, Arndt, Borst, Christoph, Brors, Benedikt, Bruns, Philipp, Carrillo de Santa Pau, Enrique, Claviez, Alexander, Doose, Gero, Haake, Andrea, Karsch, Dennis, Haas, Siegfried, Hansmann, Martin-Leo, Hoell, Jessica I., Hovestadt, Volker, Huang, Bingding, Hummel, Michael, Jäger-Schmidt, Christina, Kerssemakers, Jules N. A., Korbel, Jan O., Kube, Dieter, Lawerenz, Chris, Lenze, Dido, Martens, Joost H. A., Ott, German, Radlwimmer, Bernhard, Reisinger, Eva, Richter, Julia, Rico, Daniel, Rosenstiel, Philip, Rosenwald, Andreas, Schillhabel, Markus, Stilgenbauer, Stephan, Stadler, Peter F., Martín-Subero, José I., Szczepanowski, Monika, Warsow, Gregor, Weniger, Marc A., Zapatka, Marc, Valencia, Alfonso, Stunnenberg, Hendrik G., Lichter, Peter, Möller, Peter, Loeffler, Markus, Eils, Roland, Klapper, Wolfram, Hoffmann, Steve, Trümper, Lorenz, Küppers, Ralf, Schlesner, Matthias, and Siebert, Reiner

Published
2021
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47. The whole-genome landscape of medulloblastoma subtypes

Author

Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, and Lichter, Peter

Subjects
Cancer, Human Genome, Brain Disorders, Pediatric Cancer, Brain Cancer, Genetics, Biotechnology, Rare Diseases, Neurosciences, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Carcinogenesis, Carrier Proteins, Cohort Studies, DNA Methylation, DNA Mutational Analysis, Datasets as Topic, Epistasis, Genetic, Genome, Human, Genomics, Humans, Medulloblastoma, Molecular Targeted Therapy, Muscle Proteins, Mutation, Oncogenes, Transcription Factors, Whole Genome Sequencing, Wnt Proteins, General Science & Technology
Abstract

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Published
2017

48. Multiple inducers and novel roles of autoantibodies against the obligatory NMDAR subunit NR1: a translational study from chronic life stress to brain injury

Author

Pan, Hong, Steixner-Kumar, Agnes A., Seelbach, Anna, Deutsch, Nadine, Ronnenberg, Anja, Tapken, Daniel, von Ahsen, Nico, Mitjans, Marina, Worthmann, Hans, Trippe, Ralf, Klein-Schmidt, Christina, Schopf, Nadine, Rentzsch, Kristin, Begemann, Martin, Wienands, Jürgen, Stöcker, Winfried, Weissenborn, Karin, Hollmann, Michael, Nave, Klaus-Armin, Lühder, Fred, and Ehrenreich, Hannelore

Published
2021
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50. Large-scale automated emission measurement of individual vehicles with point sampling.

Author

Knoll, Markus, Penz, Martin, Juchem, Hannes, Schmidt, Christina, Pöhler, Denis, and Bergmann, Alexander

Subjects
EMISSION standards, PARTICULATE matter, SOOT, CARBON-black, CITIES & towns, REMOTE sensing
Abstract

Currently, emissions from internal combustion vehicles are not properly monitored throughout their life cycle. In particular, a small share of vehicles (< 20 %) with malfunctioning after-treatment systems and old vehicles with outdated engine technology are responsible for the majority (60 %–90 %) of traffic-related emissions. Remote emission sensing (RES) is a method used for screening emissions from a large number of in-use vehicles. Commercial open-path RES systems are capable of providing emission factors for many gaseous compounds, but they are less accurate and reliable for particulate matter (PM). Point sampling (PS) is an extractive RES method where a portion of the exhaust is sampled and then analyzed. So far, PS studies have been predominantly conducted on a rather small scale and have mainly analyzed heavy-duty vehicles (HDVs), which have high exhaust flow rates. In this work, we present a comprehensive PS system that can be used for large-scale screening of PM and gas emissions, largely independent of the vehicle type. The data analysis framework developed here is capable of processing data from thousands of vehicles. The core of the data analysis is our peak detection algorithm (TUG-PDA), which determines and separates emissions down to a spacing of just a few seconds between vehicles. We present a detailed evaluation of the main influencing factors on PS measurements by using about 100 000 vehicle records collected from several measurement locations, mainly in urban areas. We show the capability of the emission screening by providing real-world black carbon (BC), particle number (PN) and nitrogen oxide (NOx) emission trends for various vehicle categories such as diesel and petrol passenger cars or HDVs. Comparisons with open-path RES and PS studies show overall good agreement and demonstrate the applicability even for the latest Euro emission standards, where current open-path RES systems reach their limits. [ABSTRACT FROM AUTHOR]

Published
2024
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