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3. Nose-to-brain transport of aerosolised quantum dots following acute exposure

Author

Hopkins, Laurie E, Patchin, Esther S, Chiu, Po-Lin, Brandenberger, Christina, Smiley-Jewell, Suzette, and Pinkerton, Kent E

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Engineering, Nanotechnology, Neurosciences, Bioengineering, Neurological, Administration, Inhalation, Administration, Intranasal, Aerosols, Animals, Mice, Mice, Inbred C57BL, Microglia, Nasal Cavity, Olfactory Bulb, Olfactory Mucosa, Particle Size, Quantum Dots, qdots, olfactory epithelium, olfactory bulb, inhalation, Biomedical Engineering, Toxicology, Medical biotechnology
Abstract

Nanoparticles are of wide interest due to their potential use for diverse commercial applications. Quantum dots (QDs) are semiconductor nanocrystals possessing unique optical and electrical properties. Although QDs are commonly made of cadmium, a metal known to have neurological effects, potential transport of QDs directly to the brain has not been assessed. This study evaluated whether QDs (CdSe/ZnS nanocrystals) could be transported from the olfactory tract to the brain via inhalation. Adult C57BL/6 mice were exposed to an aerosol of QDs for 1 h via nasal inhalation, and nanoparticles were detected 3 h post-exposure within the olfactory tract and olfactory bulb by a wide range of techniques, including visualisation via fluorescent and transmission electron microscopy. We conclude that, following short-term inhalation of solid QD nanoparticles, there is rapid olfactory uptake and axonal transport to the brain/olfactory bulb with observed activation of microglial cells, indicating a pro-inflammatory response. To our knowledge, this is the first study to clearly demonstrate that QDs can be rapidly transported from the nose to the brain by olfactory uptake via axonal transport following inhalation.

Published
2014

4. Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction

Author

Schimmel, Katharina, Jung, Mira, Foinquinos, Ariana, José, Gorka San, Beaumont, Javier, Bock, Katharina, Grote-Levi, Lea, Xiao, Ke, Bär, Christian, Pfanne, Angelika, Just, Annette, Zimmer, Karina, Ngoy, Soeun, López, Begoña, Ravassa, Susana, Samolovac, Sabine, Janssen-Peters, Heike, Remke, Janet, Scherf, Kristian, Dangwal, Seema, Piccoli, Maria-Teresa, Kleemiss, Felix, Kreutzer, Fabian Philipp, Kenneweg, Franziska, Leonardy, Julia, Hobuß, Lisa, Santer, Laura, Do, Quoc-Tuan, Geffers, Robert, Braesen, Jan Hinrich, Schmitz, Jessica, Brandenberger, Christina, Müller, Dominik N., Wilck, Nicola, Kaever, Volkhard, Bähre, Heike, Batkai, Sandor, Fiedler, Jan, Alexander, Kevin M., Wertheim, Bradley M., Fisch, Sudeshna, Liao, Ronglih, Diez, Javier, González, Arantxa, and Thum, Thomas

Published
2020
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11. Hepatocellular Carcinoma Is a Natural Target for Adeno-Associated Virus (AAV) 2 Vectors

Author

Meumann, Nadja, Schmithals, Christian, Elenschneider, Leroy, Hansen, Tanja, Balakrishnan, Asha, Hu, Qingluan, Hook, Sebastian, Schmitz, Jessica, Bräsen, Jan Hinrich, Franke, Ann-Christin, Olarewaju, Olaniyi, Brandenberger, Christina, Talbot, Steven R., Fangmann, Josef, Hacker, Ulrich T., Odenthal, Margarete, Ott, Michael, Piiper, Albrecht, Büning, Hildegard, Meumann, Nadja, Schmithals, Christian, Elenschneider, Leroy, Hansen, Tanja, Balakrishnan, Asha, Hu, Qingluan, Hook, Sebastian, Schmitz, Jessica, Bräsen, Jan Hinrich, Franke, Ann-Christin, Olarewaju, Olaniyi, Brandenberger, Christina, Talbot, Steven R., Fangmann, Josef, Hacker, Ulrich T., Odenthal, Margarete, Ott, Michael, Piiper, Albrecht, and Büning, Hildegard

Abstract

Simple Summary Gene therapy is a novel approach to treat diseases by introducing corrective genetic information into target cells. Adeno-associated virus vectors are the most frequently applied gene delivery tools for in vivo gene therapy and are also studied as part of innovative anticancer strategies. Here, we report on the natural preference of AAV2 vectors for hepatocellular carcinoma (HCC) compared to nonmalignant liver cells in mice and human tissue. This preference in transduction is due to the improved intracellular processing of AAV2 vectors in HCC, resulting in significantly more vector genomes serving as templates for transcription in the cell nucleus. Based on this natural tropism for HCC, novel therapeutic strategies can be designed or existing therapeutic approaches can be strengthened as they currently result in only a minor improvement of the poor prognosis for most liver cancer patients. Abstract Although therapeutic options are gradually improving, the overall prognosis for patients with hepatocellular carcinoma (HCC) is still poor. Gene therapy-based strategies are developed to complement the therapeutic armamentarium, both in early and late-stage disease. For efficient delivery of transgenes with antitumor activity, vectors demonstrating preferred tumor tropism are required. Here, we report on the natural tropism of adeno-associated virus (AAV) serotype 2 vectors for HCC. When applied intravenously in transgenic HCC mouse models, similar amounts of vectors were detected in the liver and liver tumor tissue. In contrast, transduction efficiency, as indicated by the level of transgene product, was moderate in the liver but was elevated up to 19-fold in mouse tumor tissue. Preferred transduction of HCC compared to hepatocytes was confirmed in precision-cut liver slices from human patient samples. Our mechanistic studies revealed that this preference is due to the improved intracellular processing of AAV2 vectors in HCC, resulting, for example, in nea

Published
2022

12. Additional file 1 of Role of matrix metalloprotease-2 and MMP-9 in experimental lung fibrosis in mice

Author

Bormann, Tina, Maus, Regina, Stolper, Jennifer, Tort Tarrés, Meritxell, Brandenberger, Christina, Wedekind, Dirk, Jonigk, Danny, Welte, Tobias, Gauldie, Jack, Kolb, Martin, and Maus, Ulrich A.

Abstract

Additional file 1: Figure S1. Genotyping of MMP-2 KO, MMP-9 KO, and MMP-2/-9 double KO mice. Schematic overview of genotyping of MMP-2 KO and MMP-9 KO mice and genotyping of MMP-2 KO, MMP-9 KO, and MMP-2/-9 double KO mice by PCR. Table S1. Patient characteristics. Characteristics of ILD-patients and disease controls.

Published
2022
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14. Hepatocellular Carcinoma Is a Natural Target for Adeno-Associated Virus (AAV) 2 Vectors

Author

Meumann, Nadja, primary, Schmithals, Christian, additional, Elenschneider, Leroy, additional, Hansen, Tanja, additional, Balakrishnan, Asha, additional, Hu, Qingluan, additional, Hook, Sebastian, additional, Schmitz, Jessica, additional, Bräsen, Jan Hinrich, additional, Franke, Ann-Christin, additional, Olarewaju, Olaniyi, additional, Brandenberger, Christina, additional, Talbot, Steven R., additional, Fangmann, Josef, additional, Hacker, Ulrich T., additional, Odenthal, Margarete, additional, Ott, Michael, additional, Piiper, Albrecht, additional, and Büning, Hildegard, additional

Published
2022
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19. How to Notice a Tsunami in a Water Tank: Joint Discoveries in a Science Center

Author

Kesselheim, Klaus Wolfgang, Brandenberger, Christina, Hottiger, Christoph, and University of Zurich

Subjects
noticing, 400 Language, UFSP13-3 Language and Space, science center, 410 Linguistics, 430 German & related languages, video studies, Ethnomethodology, contextualization, discovery, Conversation Analysis, multimodality
Published
2021

20. Nicotinamide for the treatment of heart failure with preserved ejection fraction

Author

Abdellatif, Mahmoud, Trummer-Herbst, Viktoria, Koser, Franziska, Durand, Sylvere, Adao, Rui, Vasques-Novoa, Francisco, Freundt, Johanna K., Voglhuber, Julia, Pricolo, Maria-Rosaria, Kasa, Michael, Turk, Clara, Aprahamian, Fanny, Herrero-Galan, Elias, Hofer, Sebastian J., Pendl, Tobias, Rech, Lavinia, Kargl, Julia, Anto-Michel, Nathaly, Ljubojevic-Holzer, Senka, Schipke, Julia, Brandenberger, Christina, Auer, Martina, Schreiber, Renate, Koyani, Chintan N., Heinemann, Akos, Zirlik, Andreas, Schmidt, Albrecht, von Lewinski, Dirk, Scherr, Daniel, Rainer, Peter P., von Maltzahn, Julia, Muhlfeld, Christian, Kruger, Marcus, Frank, Sasa, Madeo, Frank, Eisenberg, Tobias, Prokesch, Andreas, Leite-Moreira, Adelino F., Lourenco, Andre P., Alegre-Cebollada, Jorge, Kiechl, Stefan, Linke, Wolfgang A., Kroemer, Guido, Sedej, Simon, Abdellatif, Mahmoud, Trummer-Herbst, Viktoria, Koser, Franziska, Durand, Sylvere, Adao, Rui, Vasques-Novoa, Francisco, Freundt, Johanna K., Voglhuber, Julia, Pricolo, Maria-Rosaria, Kasa, Michael, Turk, Clara, Aprahamian, Fanny, Herrero-Galan, Elias, Hofer, Sebastian J., Pendl, Tobias, Rech, Lavinia, Kargl, Julia, Anto-Michel, Nathaly, Ljubojevic-Holzer, Senka, Schipke, Julia, Brandenberger, Christina, Auer, Martina, Schreiber, Renate, Koyani, Chintan N., Heinemann, Akos, Zirlik, Andreas, Schmidt, Albrecht, von Lewinski, Dirk, Scherr, Daniel, Rainer, Peter P., von Maltzahn, Julia, Muhlfeld, Christian, Kruger, Marcus, Frank, Sasa, Madeo, Frank, Eisenberg, Tobias, Prokesch, Andreas, Leite-Moreira, Adelino F., Lourenco, Andre P., Alegre-Cebollada, Jorge, Kiechl, Stefan, Linke, Wolfgang A., Kroemer, Guido, and Sedej, Simon

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD(+)). Elevating NAD(+) by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD(+) precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD(+) precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans.

Published
2021

21. Telomerase therapy attenuates cardiotoxic effects of doxorubicin

Author

Chatterjee, Shambhabi, primary, Hofer, Teresa, additional, Costa, Alessia, additional, Lu, Dongchao, additional, Batkai, Sandor, additional, Gupta, Shashi Kumar, additional, Bolesani, Emiliano, additional, Zweigerdt, Robert, additional, Megias, Diego, additional, Streckfuss-Bömeke, Katrin, additional, Brandenberger, Christina, additional, Thum, Thomas, additional, and Bär, Christian, additional

Published
2021
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22. Rescue from Pseudomonas aeruginosa Airway Infection via Stem Cell Transplantation

Author

Brinkert, Kerstin, primary, Hedtfeld, Silke, additional, Burhop, Annina, additional, Gastmeier, Rena, additional, Gad, Pauline, additional, Wedekind, Dirk, additional, Kloth, Christina, additional, Rothschuh, Justin, additional, Lachmann, Nico, additional, Hetzel, Miriam, additional, Jirmo, Adan Chari, additional, Lopez-Rodriguez, Elena, additional, Brandenberger, Christina, additional, Hansen, Gesine, additional, Schambach, Axel, additional, Ackermann, Mania, additional, Tümmler, Burkhard, additional, and Munder, Antje, additional

Published
2021
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23. Supplemental information on scRNA-seq data. Yazicioglu et al. 2020 AJP Lung

Author

Yazicioglu, Tolga, Mühlfeld, Christian, Autilio, Chiara, Huang, Cheng-Kai, Bär, Christian, Dittrich-Breiholz, Oliver, Thum, Thomas, Perez-Gil, Jesus, Schmiedl, Andreas, and Brandenberger, Christina

Abstract

Supplemental file 1: Global comparison analysis in AE2 of all four exposure groups performed in Loupe browser; showing average and log2-fold expression as well as corresponding p-values for each exposure groupSupplemental file 2: Comparison analysis between young control and young 24 h LPS AE2 gene expression performed in Loupe browser; showing average and log2-fold expression in both experimental groups and corresponding p-values (Supplemental file 3: Comparison analysis between old control and old 24 h LPS AE2 gene expression performed in Loupe browser; showing average and log2-fold expression in both experimental groups and corresponding p-values (Supplemental file 4: Comparison analysis between young control and old control AE2 gene expression performed in Loupe browser; showing average and log2-fold expression of both experimental groups and corresponding p-values (Supplemental file 5: Comparison analysis between young 24 h LPS and old 24 h LPS AE2 gene expression performed in Loupe browser; showing average and log2-fold expression in both experimental groups and corresponding p-values (Supplemental figure 1: Different assigned cell populations within scRNA-seq analysis of isolated, EpCAM positive lungSupplemental figure 2: Heat-map and expression profiles of selected genes (Cdnk1a and Trp53) in AE2 of second data setSupplemental figure 3: Expression profile of H2afx (yH2AX) in AE2 of all experimental groups

Published
2020
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24. Sharing perception when using hands-on exhibits in science centres: the case of vocal depiction

Author

Brandenberger, Christina, Hottiger, Christoph, University of Zurich, Gonzalez, Sylvia, Skogmyr Marian, Klara, Volpin, Letizia, Gfeller, Fabienne, Bietti, Lucas, and Bangerter, Adrian

Subjects
400 Language, UFSP13-3 Language and Space, 410 Linguistics
Abstract

There are various situations in our daily lives in which we share sensory perceptions in interaction, but research on how exactly we do this is relatively scarce and has often focused primarily on the visual and auditory channels. In this paper, we suggest an approach based on the methods of multimodal conversation analysis which also considers other perceptual fields, especially touch. By means of an example from an interaction between two visitors of a science centre and the way they handle an exhibit, we illustrate how one can approach the analysis of the techniques participants use to make their sensory perceptions available to their interactive partners. We will focus on one such technique, namely the vocal depiction of tactile perceptions.

Published
2018

30. Intracellular imaging of nanoparticles: Is it an elemental mistake to believe what you see?

Author

Mühlfeld Christian, Vanhecke Dimitri, Clift Martin JD, Brandenberger Christina, Stone Vicki, Gehr Peter, and Rothen-Rutishauser Barbara

Subjects
Toxicology. Poisons, RA1190-1270, Industrial hygiene. Industrial welfare, HD7260-7780.8
Abstract

Abstract In order to understand how nanoparticles (NPs J774.A1 murine macrophage-like cells were exposed to NH2 polyethylene (PEG) QDs and elemental co-localization analysis of two elements present in the QDs (sulfur and cadmium) was performed on putative intracellular QDs with electron spectroscopic imaging (ESI). Both elements were shown on a single particle level and QDs were confirmed to be located inside intracellular vesicles. Nevertheless, ESI analysis showed that not all nano-sized structures, initially identified as QDs, were confirmed. This observation emphasizes the necessity to perform elemental analysis when investigating intracellular NP localization using TEM.

Published
2010
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31. A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles

Author

Ferron George A, Schulz Holger, Rothen-Rutishauser Barbara, Brandenberger Christina, Dittrich Vlad, Lentner Bernd, Karg Erwin, Lenz Anke, and Schmid Otmar

Subjects
Toxicology. Poisons, RA1190-1270, Industrial hygiene. Industrial welfare, HD7260-7780.8
Abstract

Abstract Background Engineered nanoparticles are becoming increasingly ubiquitous and their toxicological effects on human health, as well as on the ecosystem, have become a concern. Since initial contact with nanoparticles occurs at the epithelium in the lungs (or skin, or eyes), in vitro cell studies with nanoparticles require dose-controlled systems for delivery of nanoparticles to epithelial cells cultured at the air-liquid interface. Results A novel air-liquid interface cell exposure system (ALICE) for nanoparticles in liquids is presented and validated. The ALICE generates a dense cloud of droplets with a vibrating membrane nebulizer and utilizes combined cloud settling and single particle sedimentation for fast (~10 min; entire exposure), repeatable (2. The cell-specific deposition efficiency is currently limited to 0.072 (7.2% for two commercially available 6-er transwell plates), but a deposition efficiency of up to 0.57 (57%) is possible for better cell coverage of the exposure chamber. Dose-response measurements with ZnO nanoparticles (0.3-8.5 μg/cm2) showed significant differences in mRNA expression of pro-inflammatory (IL-8) and oxidative stress (HO-1) markers when comparing submerged and air-liquid interface exposures. Both exposure methods showed no cellular response below 1 μg/cm2 ZnO, which indicates that ZnO nanoparticles are not toxic at occupationally allowed exposure levels. Conclusion The ALICE is a useful tool for dose-controlled nanoparticle (or solute) exposure of cells at the air-liquid interface. Significant differences between cellular response after ZnO nanoparticle exposure under submerged and air-liquid interface conditions suggest that pharmaceutical and toxicological studies with inhaled (nano-)particles should be performed under the more realistic air-liquid interface, rather than submerged cell conditions.

Published
2009
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32. Particles induce apical plasma membrane enlargement in epithelial lung cell line depending on particle surface area dose

Author

Blank Fabian, Rothen-Rutishauser Barbara, Brandenberger Christina, Gehr Peter, and Mühlfeld Christian

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Airborne particles entering the respiratory tract may interact with the apical plasma membrane (APM) of epithelial cells and enter them. Differences in the entering mechanisms of fine (between 0.1 μm and 2.5 μm) and ultrafine ( ≤ 0.1 μm) particles may be associated with different effects on the APM. Therefore, we studied particle-induced changes in APM surface area in relation to applied and intracellular particle size, surface and number. Methods Human pulmonary epithelial cells (A549 cell line) were incubated with various concentrations of different sized fluorescent polystyrene spheres without surface charge (∅ fine – 1.062 μm, ultrafine – 0.041 μm) by submersed exposure for 24 h. APM surface area of A549 cells was estimated by design-based stereology and transmission electron microscopy. Intracellular particles were visualized and quantified by confocal laser scanning microscopy. Results Particle exposure induced an increase in APM surface area compared to negative control (p < 0.01) at the same surface area concentration of fine and ultrafine particles a finding not observed at low particle concentrations. Ultrafine particle entering was less pronounced than fine particle entering into epithelial cells, however, at the same particle surface area dose, the number of intracellular ultrafine particles was higher than that of fine particles. The number of intracellular particles showed a stronger increase for fine than for ultrafine particles at rising particle concentrations. Conclusion This study demonstrates a particle-induced enlargement of the APM surface area of a pulmonary epithelial cell line, depending on particle surface area dose. Particle uptake by epithelial cells does not seem to be responsible for this effect. We propose that direct interactions between particle surface area and cell membrane cause the enlargement of the APM.

Published
2009
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33. Localization of Exogenous Mesenchymal Stem Cells in a Pig Model of Lung Transplantation

Author

Piatkowski, Tanja, Brandenberger, Christina, Rahmanian, Parwis, Choi, Yeong-Hoon, Zeriouh, Mohamed, Sabashnikov, Anton, Wittwer, Thorsten, Wahlers, Thorsten C. W., Ochs, Matthias, Muehlfeld, Christian, Piatkowski, Tanja, Brandenberger, Christina, Rahmanian, Parwis, Choi, Yeong-Hoon, Zeriouh, Mohamed, Sabashnikov, Anton, Wittwer, Thorsten, Wahlers, Thorsten C. W., Ochs, Matthias, and Muehlfeld, Christian

Abstract

Background Mesenchymal stem cells (MSCs) have a great potential for the treatment of acute lung injury. This study provides a detailed immunohistochemical and stereological analysis of the localization and distribution of exogenous MSC in a pig model of lung transplantation after intravascular or endobronchial application. Methods MSC derived from human bone marrow were labeled by DiI and administered intravascularly or endobronchially to the lungs of donor pigs after a period of 3 hours warm and 3 hours cold ischemia. The left lung was transplanted to a recipient pig and reperfused for 4 hours before fixation. The right donor lung was fixed for microscopic analysis directly after the ischemia time. Results After both administration routes, a similar number of exogenous MSC was found in the lungs. Within each animal, the heterogeneity of MSC distribution was high both with respect to left and right lung as well as to the different lobes of each lung. After endobronchial application, MSC were found in alveolar and bronchial/bronchiolar lumen, whereas after intravascular administration, they were mainly observed in blood vessels. Conclusion Although the administration of exogenous MSC is possible by endobronchial or intravascular application, it yields a heterogeneous distribution in the lungs which may warrant strategies to improve a more homogeneous distribution.

Published
2018

34. Aging impairs alveolar epithelial type II cell function in acute lung injury.

Author

Tolga Yazicioglu, Mühlfeld, Christian, Autilio, Chiara, Cheng-Kai Huang, Bär, Christian, Dittrich-Breiholz, Oliver, Thum, Thomas, Pérez-Gil, Jesús, Schmiedl, Andreas, and Brandenberger, Christina

Subjects
LUNG injuries, CELLULAR aging, CELL physiology, RNA sequencing, INFLAMMATION, AGING
Abstract

Morbidity and mortality rates in acute lung injury (ALI) increase with age. As alveolar epithelial type II cells (AE2) are crucial for lung function and repair, we hypothesized that aging promotes senescence in AE2 and contributes to the severity and impaired regeneration in ALI. ALI was induced with 2.5 g lipopolysaccharide/g body weight in young (3 mo) and old (18 mo) mice that were euthanized 24 h, 72 h, and 10 days later. Lung function, pulmonary surfactant activity, stereology, cell senescence, and singlecell RNA sequencing analyses were performed to investigate AE2 function in aging and ALI. In old mice, surfactant activity was severely impaired. A 60% mortality rate and lung function decline were observed in old, but not in young, mice with ALI. AE2 of young mice adapted to injury by increasing intracellular surfactant volume and proliferation rate. In old mice, however, this adaptive response was compromised, and AE2 of old mice showed signs of cell senescence, increased inflammatory signaling, and impaired surfactant metabolism in ALI. These findings provide evidence that ALI promotes a limited proliferation rate, increased inflammatory response, and surfactant dysfunction in old, but not in young, mice, supporting an impaired regenerative capacity and reduced survival rate in ALI with advancing age. [ABSTRACT FROM AUTHOR]

Published
2020
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35. Dietary Docosahexaenoic Acid Prevents Silica-Induced Development of Pulmonary Ectopic Germinal Centers and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse

Author

Bates, Melissa A., primary, Akbari, Peyman, additional, Gilley, Kristen N., additional, Wagner, James G., additional, Li, Ning, additional, Kopec, Anna K., additional, Wierenga, Kathryn A., additional, Jackson-Humbles, Daven, additional, Brandenberger, Christina, additional, Holian, Andrij, additional, Benninghoff, Abby D., additional, Harkema, Jack R., additional, and Pestka, James J., additional

Published
2018
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37. Rescue from Pseudomonas aeruginosaAirway Infection via Stem Cell Transplantation

Author

Brinkert, Kerstin, Hedtfeld, Silke, Burhop, Annina, Gastmeier, Rena, Gad, Pauline, Wedekind, Dirk, Kloth, Christina, Rothschuh, Justin, Lachmann, Nico, Hetzel, Miriam, Jirmo, Adan Chari, Lopez-Rodriguez, Elena, Brandenberger, Christina, Hansen, Gesine, Schambach, Axel, Ackermann, Mania, Tümmler, Burkhard, and Munder, Antje

Abstract

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to impaired ion transport in epithelial cells. Although lung failure due to chronic infection is the major comorbidity in individuals with cystic fibrosis, the role of CFTR in non-epithelial cells has not been definitively resolved. Given the important role of host defense cells, we evaluated the Cftr deficiency in pulmonary immune cells by hematopoietic stem cell transplantation in cystic fibrosis mice. We transplanted healthy bone marrow stem cells and could reveal a stable chimerism of wild-type cells in peripheral blood. The outcome of stem cell transplantation and the impact of healthy immune cells were evaluated in acute Pseudomonas aeruginosaairway infection. In this study, mice transplanted with wild-type cells displayed better survival, lower lung bacterial numbers, and a milder disease course. This improved physiology of infected mice correlated with successful intrapulmonary engraftment of graft-derived alveolar macrophages, as seen by immunofluorescence microscopy and flow cytometry of graft-specific leucocyte surface marker CD45 and macrophage marker CD68. Given the beneficial effect of hematopoietic stem cell transplantation and stable engraftment of monocyte-derived CD68-positive macrophages, we conclude that replacement of mutant Cftr macrophages attenuates airway infection in cystic fibrosis mice.

Published
2021
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38. Sharing perception when using hands-on exhibits in science centres: The case of vocal depiction

Author

Gonzalez, Sylvia, Skogmyr Marian, Klara, Volpin, Letizia, Gfeller, Fabienne, Bietti, Lucas, Bangerter, Adrian, Gonzalez, S ( Sylvia ), Skogmyr Marian, K ( Klara ), Volpin, L ( Letizia ), Gfeller, F ( Fabienne ), Bietti, L ( Lucas ), Bangerter, A ( Adrian ), Brandenberger, Christina; https://orcid.org/0000-0002-1289-0384, Hottiger, Christoph; https://orcid.org/0000-0001-8942-1159, Gonzalez, Sylvia, Skogmyr Marian, Klara, Volpin, Letizia, Gfeller, Fabienne, Bietti, Lucas, Bangerter, Adrian, Gonzalez, S ( Sylvia ), Skogmyr Marian, K ( Klara ), Volpin, L ( Letizia ), Gfeller, F ( Fabienne ), Bietti, L ( Lucas ), Bangerter, A ( Adrian ), Brandenberger, Christina; https://orcid.org/0000-0002-1289-0384, and Hottiger, Christoph; https://orcid.org/0000-0001-8942-1159

Abstract

There are various situations in our daily lives in which we share sensory perceptions in interaction, but research on how exactly we do this is relatively scarce and has often focused primarily on the visual and auditory channels. In this paper, we suggest an approach based on the methods of multimodal conversation analysis which also considers other perceptual fields, especially touch. By means of an example from an interaction between two visitors of a science centre and the way they handle an exhibit, we illustrate how one can approach the analysis of the techniques participants use to make their sensory perceptions available to their interactive partners. We will focus on one such technique, namely the vocal depiction of tactile perceptions.

Published
2017

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