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1. A Colonic Organoid Model Challenged with the Large Toxins of Clostridioides difficile TcdA and TcdB Exhibit Deregulated Tight Junction Proteins

Author

Martina Schneemann, Lucas Heils, Verena Moos, Franziska Weiß, Susanne M. Krug, January Weiner, Dieter Beule, Ralf Gerhard, Jörg-Dieter Schulzke, and Roland Bücker

Subjects
intestinal epithelial human colonic organoid monolayer, claudin, leak flux diarrhea, leaky gut, super-resolution STED microscopy, tricellulin, Medicine
Abstract

Background: Clostridioides difficile toxins TcdA and TcdB are responsible for diarrhea and colitis. Lack of functional studies in organoid models of the gut prompted us to elucidate the toxin’s effects on epithelial barrier function and the molecular mechanisms for diarrhea and inflammation. Methods: Human adult colon organoids were cultured on membrane inserts. Tight junction (TJ) proteins and actin cytoskeleton were analyzed for expression via Western blotting and via confocal laser-scanning microscopy for subcellular localization. Results: Polarized intestinal organoid monolayers were established from stem cell-containing colon organoids to apply toxins from the apical side and to perform functional measurements in the organoid model. The toxins caused a reduction in transepithelial electrical resistance in human colonic organoid monolayers with sublethal concentrations. Concomitantly, we detected increased paracellular permeability fluorescein and FITC-dextran-4000. Human colonic organoid monolayers exposed to the toxins exhibited redistribution of barrier-forming TJ proteins claudin-1, -4 and tricellulin, whereas channel-forming claudin-2 expression was increased. Perijunctional F-actin cytoskeleton organization was affected. Conclusions: Adult stem cell-derived human colonic organoid monolayers were applicable as a colon infection model for electrophysiological measurements. The TJ changes noted can explain the epithelial barrier dysfunction and diarrhea in patients, as well as increased entry of luminal antigens triggering inflammation.

Published
2023
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3. CDT of Clostridioides difficile Induces MLC-Dependent Intestinal Barrier Dysfunction in HT-29/B6 Epithelial Cell Monolayers

Author

Lucas Heils, Martina Schneemann, Ralf Gerhard, Jörg-Dieter Schulzke, and Roland Bücker

Subjects
binary toxin, tight junction, barrier function, claudin, tricellulin, occludin, Medicine
Abstract

Background: Clostridioides difficile binary toxin (CDT) defines the hypervirulence of strains in nosocomial antibiotic-induced colitis with the highest mortality. The objective of our study was to investigate the impact of CDT on the intestinal epithelial barrier and to enlighten the underlying molecular mechanisms. Methods: Functional measurements of epithelial barrier function by macromolecular permeability and electrophysiology were performed in human intestinal HT-29/B6 cell monolayers. Molecular analysis of the spatial distribution of tight junction protein and cytoskeleton was performed by super-resolution STED microscopy. Results: Sublethal concentrations of CDT-induced barrier dysfunction with decreased TER and increased permeability for 332 Da fluorescein and 4 kDa FITC-dextran. The molecular correlate to the functional barrier defect by CDT was found to be a tight junction protein subcellular redistribution with tricellulin, occludin, and claudin-4 off the tight junction domain. This redistribution was shown to be MLCK-dependent. Conclusions: CDT compromised epithelial barrier function in a human intestinal colonic cell model, even in sublethal concentrations, pointing to barrier dysfunction in the intestine and leak flux induction as a diarrheal mechanism. However, this cannot be attributed to the appearance of apoptosis and necrosis, but rather to an opening of the paracellular leak pathway as the result of epithelial tight junction alterations.

Published
2023
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7. Reading, Metacognition and Motivation: A Follow-Up Study of German Students in Grades 7 and 8

Author

Roeschl-Heils, Annette, Schneider, Wolfgang, and van Kraayenoord, Christina E.

Abstract

This follow-up study to van Kraayenoord and Schneider (1999) examined the performance in reading, metacognition and motivation related to reading of students in Grades 7 and 8. Results showed significant correlations between all of the variables. A multivariate analysis of variance showed that "good" and "poor" readers differed in reading self-concept and metacognitive measures related to reading and memory. A stepwise regression analysis suggested that the metacognitive variables were the best predictors of reading. Furthermore, a comparison of the results of the previous study with those of the current investigation revealed that the findings were stable over time. Since the period between the two studies is the time during which students make important decisions related to enrolment in one of three distinct school-types in Germany, we examined the results of various groups of students: those in "Gymnasium" (high educational track), "Realschule" (middle educational track), and "Hauptschule" (low educational track). Students in the Gymnasium scored significantly better than students in the other two groups on almost all variables related to reading. A re-analysis of the data from our first investigation found that the results of the Gymnasium students in the second study could be predicted from their results obtained during elementary school. (Contains 3 tables.)

Published
2003

8. Prophylactic Salpingectomy during Hysterectomy for Benign Disease: A Prospective Study to Evaluate High-Grade Serous Ovarian Carcinoma Precursors

Author

Garri Tchartchian, Bernd Bojahr, Lucas Heils, Harald Krentel, and Rudy L. De Wilde

Subjects
opportunistic salpingectomy, hysterectomy, LASH, laparoscopic, p53, STIL, General Medicine
Abstract

Recent findings suggest that high-grade serous ovarian cancer can originate in the fallopian tube. Not only has that made the identification of precursor lesions pivotal in early detection and prevention of these cancers, prophylactic salpingectomy alongside hysterectomy for benign indications has been increasingly proposed as well. The present prospective single-center study included 273 women who underwent opportunistic salpingectomy alongside laparoscopic supracervical hysterectomy. Uterine and tubal histopathological results as well as intra- and postoperative complications were evaluated. The complication rate was 3.3%, of which none were caused by salpingectomy. Uterine histopathology diagnosed 181 patients (66.8%) with uterine myomas, 60 patients (22.1%) with adenomyosis, 29 patients (10.7%) with adenomyomatosis, and, 1 patient (0.4%) without pathological abnormality. p53 signatures were detected in 221 right fallopian tubes (80.9%) and in 229 left tubes (83.9%). In total, 8 patients showed bilateral STIL (2.9%), whereas in 1 patient (0.4%) STIL was detected in the left tube only. No STIC were detected. Laparoscopic opportunistic salpingectomy is demonstrated to be both safe and feasible. It appears to be promising to reduce the risk for ovarian cancer, yet more studies are needed to undoubtedly confirm this.

Published
2022

10. Prophylactic Salpingectomy during Hysterectomy for Benign Disease: A Prospective Study to Evaluate High-Grade Serous Ovarian Carcinoma Precursors.

Author

Tchartchian, Garri, Bojahr, Bernd, Heils, Lucas, Krentel, Harald, and De Wilde, Rudy L.

Subjects
SALPINGECTOMY, HYSTERECTOMY, ECTOPIC pregnancy, OVARIAN cancer, SURGICAL complications, FALLOPIAN tubes, EARLY detection of cancer, LONGITUDINAL method
Abstract

Recent findings suggest that high-grade serous ovarian cancer can originate in the fallopian tube. Not only has that made the identification of precursor lesions pivotal in early detection and prevention of these cancers, prophylactic salpingectomy alongside hysterectomy for benign indications has been increasingly proposed as well. The present prospective single-center study included 273 women who underwent opportunistic salpingectomy alongside laparoscopic supracervical hysterectomy. Uterine and tubal histopathological results as well as intra- and postoperative complications were evaluated. The complication rate was 3.3%, of which none were caused by salpingectomy. Uterine histopathology diagnosed 181 patients (66.8%) with uterine myomas, 60 patients (22.1%) with adenomyosis, 29 patients (10.7%) with adenomyomatosis, and, 1 patient (0.4%) without pathological abnormality. p53 signatures were detected in 221 right fallopian tubes (80.9%) and in 229 left tubes (83.9%). In total, 8 patients showed bilateral STIL (2.9%), whereas in 1 patient (0.4%) STIL was detected in the left tube only. No STIC were detected. Laparoscopic opportunistic salpingectomy is demonstrated to be both safe and feasible. It appears to be promising to reduce the risk for ovarian cancer, yet more studies are needed to undoubtedly confirm this. [ABSTRACT FROM AUTHOR]

Published
2023
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13. Linkage and mutational analysis of CLCN2 in childhood absence epilepsy

Author

Everett, Kate, Chioza, Barry, Aicardi, Jean, Aschauer, Harald, Brouwer, Oebele, Callenbach, Petra, Covanis, Athanasios, Dooley, Joseph, Dulac, Olivier, Durner, Martina, Eeg-Olofsson, Orvar, Feucht, Martha, Friis, Mogens, Guerrini, Renzo, Heils, Armin, Kjeldsen, Marianne, Nabbout, Rima, Sander, Thomas, Wirrell, Elaine, McKeigue, Paul, Robinson, Robert, Taske, Nichole, and Gardiner, Mark

Published
2007
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22. Molecular manipulations as tools for enhancing our understanding of 5-HT neurotransmission

Author

Murphy, Dennis L., Wichems, Christine, Li, Qian, and Heils, Armin

Subjects
Drug metabolism -- Research, Drug receptors -- Research, Neural transmission -- Research, Biological sciences, Chemistry, Pharmaceuticals and cosmetics industries
Abstract

A developing trend in exploring the sites at which drugs act is to use molecular rather than chemical agents to alter receptors, intracellular signalling mechanisms or gene expression. The 5-HT neurotransmission system is targeted by drugs useful in many behavioural disorders, including anxiety, depression, psychosis and eating disorders. It also regulates many physiological functions and provides some examples of the potential use of these new molecular approaches. This article reviews the progress made in the molecular manipulation of 5-HT receptors and discusses the potential of such tools for the treatment of diseases associated with the 5-HT transmission system.

Published
1999

27. In Situ Separation of the Chiral Target Compound (S)-2-Pentanol in Biocatalytic Reactive Distillation

Author

Andreas Liese, Anne Stöbener, Gerrit Sluyter, Joscha Kleber, Steffen Kühn, Marc-Andreas Christlieb, Rene Heils, and Irina Smirnova

Subjects
Fractional distillation, Chromatography, biology, General Chemical Engineering, 02 engineering and technology, General Chemistry, Transesterification, 021001 nanoscience & nanotechnology, biology.organism_classification, Industrial and Manufacturing Engineering, Compound s, law.invention, Propanol, chemistry.chemical_compound, 020401 chemical engineering, chemistry, law, Reactive distillation, Organic chemistry, Candida antarctica, 0204 chemical engineering, 0210 nano-technology, Enantiomeric excess, Distillation
Abstract

In situ separation of a chiral target compound is realized for the first time as distillate on top of an integrated biocatalytic batch reactive distillation column. The applied reaction system is the racemic resolution of (R/S)-2-pentanol in a transesterification with propyl butyrate, which is catalyzed by immobilized Candida antarctica lipase B (Novozym435). Biocatalyst integration is realized in baskets of wire gauze catalytic packings as column internals. The equilibrium limited reaction is shifted to the product side by fractional distillation of low boiling propanol and the target compound (S)-2-pentanol. Increased molar fractions up to x(S)-2-PeOH = 65 ± 4% with an enantiomeric excess of 90 ± 4% and 51 ± 3% overall conversion are reached for (S)-2-pentanol. Feasibility of the reaction system is investigated in our preselection tool. This tool is developed to evaluate predefined operation conditions in the column setup for transesterification reactions based on criteria regarding biocatalyst stabilit...

Published
2017

28. An injectable alginate-based hydrogel for microfluidic applications

Author

Ozlem Yesil-Celiktas, Irina Smirnova, Seref Akay, Rene Heils, and Hoc Khiem Trieu

Subjects
Microchannel, Polymers and Plastics, Immobilized enzyme, Alginates, 010405 organic chemistry, Microfluidics, Organic Chemistry, Hydrogels, Nanotechnology, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, Chitosan, chemistry.chemical_compound, Chemical engineering, chemistry, Materials Chemistry, 0210 nano-technology, Spiral coil, Microfabrication
Abstract

The objective of this study was to develop an injectable alginate based formulation for immobilizing enzymes into microfluidic systems. The gelation was induced upon lowering the pH by addition of D-glucono-delta-lactone (GDL) and release of Ca+ ions from solid CaCO3. The effects of GDL concentration on enzymatic activity and gelation time were investigated. The results indicated that increasing the GDL concentration increased both surface area and enzymatic activity. Also, chitosan was added to the formulation at different ratios to enhance the stability of enzyme during immobilization. For microfluidic application, 100 mu l spiral coil single channel microchip was fabricated and alginate GDL mixture containing beta-glucosidase was injected to the microchannel prior to gelation. Enzymatic conversion was performed by pumping substrate (pNPG) through the microchannel. The results indicated that the entire substrate was converted continuously during 24 h without any leakage or deactivation of immobilized enzyme. (C) 2017 Elsevier Ltd. All rights reserved.

Published
2017

29. Pilot-scale validation of Enzymatic Reactive Distillation for butyl butyrate production

Author

Anton A. Kiss, Philip Lutze, Mirko Skiborowski, Irina Smirnova, Matthias Wierschem, Rene Heils, Stefan Schlimper, and Sustainable Process Technology

Subjects
Immobilized enzyme, Chemistry(all), General Chemical Engineering, Batch reactor, Process design, 02 engineering and technology, Industrial and Manufacturing Engineering, Reaction rate, chemistry.chemical_compound, 020401 chemical engineering, Environmental Chemistry, 0204 chemical engineering, Reactive distillation, Chemistry, Modeling, General Chemistry, Lipase, 021001 nanoscience & nanotechnology, n/a OA procedure, Chemical engineering, Product inhibition, Process intensification, Chemical Engineering(all), Biocatalysis, Hydrodynamics, Chemical equilibrium, 0210 nano-technology, Butyl butyrate
Abstract

For enzyme-catalyzed reactions, batch processes using stirred tank reactors are the state-of-the-art production mode. The yield of the process may be limited by reaction equilibrium, product inhibition of the enzyme, low concentrations and possibly low reaction rates, while the recovery of the product may be limited due to thermodynamic constraints such as azeotropes. Using enzymes in an integrated reactive distillation process can overcome these limitations and provides a cost advantage over classic batch reactor processes. The aim of this paper is i) to report the successful pilot-scale experimental validation of an Enzymatic Reactive Distillation (ERD) process for the synthesis of butyl butyrate and ii) to establish a rate-based model for conceptual process design which can be quickly adapted to other systems. The main novelty is the application of a continuous RD column with enzymes as a heterogeneous catalyst provided in two different types of catalytic packing: loosely filled immobilized enzyme beads in standard packings with catalyst pockets and gauze packings with catalytic coating. Experimental pilot-scale experiments show the feasibility of ERD and allow the comparison of the different packing types based on catalytic performance as well as stability. Furthermore, these experiments are used to validate a predictive rate-based model to describe ERD which can be used to check the sensitivity of process and design parameters as well as to provide a quick adaption to other systems for quick evaluation.

Published
2017

36. In situ production and renewal of biocatalytic coatings for use in enzymatic reactive distillation

Author

Xihua Hu, Andreas Liese, Rene Heils, and Irina Smirnova

Subjects
Chemical substance, Immobilized enzyme, business.industry, Chemistry, General Chemical Engineering, 02 engineering and technology, General Chemistry, Chemical industry, engineering.material, 010402 general chemistry, 01 natural sciences, Industrial and Manufacturing Engineering, 0104 chemical sciences, Catalysis, 020401 chemical engineering, Chemical engineering, Coating, Scientific method, Reactive distillation, engineering, Environmental Chemistry, Thermal stability, 0204 chemical engineering, business
Abstract

Reactive distillation is one of the most well-established integrative separation processes in chemical industry which is used for the production of e.g. fuel additives. Recently, the feasibility of enzymes in reactive distillation columns was demonstrated, which possibly extends the scope towards more selective reactions with chiral products. However, the low thermal stability of enzymes necessitates a more frequent catalyst exchange which is usually a knock-out criterion for this process due to very high costs of catalytic structures and long process shut down times. In this work, an in situ production method for biocatalytic coatings on structured packings is presented which enables production and renewal of the catalytic structures in place, i.e. without disassembly of the column internals. By flooding the column with reacting enzyme/silica-sol, gauze structured packings are covered with a uniform layer of gel, which after drying results in a catalytic coating containing immobilized enzymes. The in situ method could help simplify the catalyst exchange in reactive distillation processes and furthermore allows changes in the reactive section in terms of amount and position of the catalyst which are important process parameters in the design phase of reactive distillation processes. Video: For a video showing the in situ procedure, please see Supplementary data .

Published
2016

38. A Multicenter Study of BRD2 as a Risk Factor for Juvenile Myoclonic Epilepsy

Author

Cavalleri, Gianpiero L., Walley, Nicole M., Soranzo, Nicole, Mulley, John, Doherty, Colin P., Kapoor, Ashish, Depondt, Chantal, Lynch, John M., Scheffer, Ingrid E., Heils, Armin, Gehrmann, Anne, Kinirons, Peter, Gandhi, Sonia, Satishchandra, Parthasarathy, Wood, Nicholas W., Anand, Anuranjan, Sander, Thomas, Berkovic, Samuel F., Delanty, Norman, Goldstein, David B., and Sisodiya, Sanjay M.

Published
2007

40. Abstracts Second Congress of the European Society for Clinical Neuropharmacology: Würzburg, November 9–11, 1995

Author

Agid, Y., Arendt, T., Gärtner, U., Holzer, M., Fruth, P., Brückner, M. K., Arzberger, T., Weindl, A., Baas, H., Demisch, L., Harder, S., Bürklin, F., Fischer, P. A., Bagli, M., Rao, M. L., Sobanski, T., Laux, G., Barbier, P., Fumagalli, F., Donati, E., Maggio, R., Racagni, G., Corsini, G. U., Riva, M., Berger, J., Löschl, B., Bernheimer, H., Lugowska, A., Tylki-Szymanska, A., Gieselmann, V., Molzer, B., Faé, I., Bernocchi, G., Scherini, E., Necchi, D., Bigl, M., Bleyl, D., Bigl, V., Eschrich, K., Block, F., Schwarz, M., Blum-Degen, D., Müller, Th., Kuhn, W., Gerlach, M., Przuntek, H., Riederer, R., Bonuccelli, U., Ceravolo, R., Nuti, A., D'Avino, C., Placidi, G., Perugi, G., Cassano, G. B., Del Dotto, P., Piccini, P., Colzi, A., Muratorio, A., Braak, H., Braak, E., Yilmazer, D. M., de Vos, R. A. I., Jansen, E. N. H., Bringmann, G., Clement, H. W., Grote, C., Rausch, F., Reichmann, H., Riederer, P., Sontag, K. -H., Wesemann, W., God, R., Feineis, D., Brückner, R., Protzen, J. -A., Fähr, S., Rausch, W. -D., Brunt, E. R. P., Pruim, J., Willemsen, A. J., van Weerden, T. W., Bryan-Lluka, L. J., Bönisch, H., Büttner, Th., Kühn, W., McMonagle, U., Calza, L., Pozza, M., Coraddu, F., Farci, G., Carlsson, A., Napolitano, A., Salvetti, S., Dell'Agnello, G., Renna, M., Conquet, F., Bashir, Z., Daniel, H., Ferraguti, F., Collingridge, G., Crépel, F., Coos Verhoef, J., Merkus, F. W. H. M., Junginger, H. E., Cruz-Sánchez, F. F., Kutschka, T., Beeg, M., Deuschle, M., Weber, B., Körner, A., Standhardt, H., Lammers, C. -H., Motzek-Noé, T., Heuser, I., Earl, C. D., Reum, T., Sautter, J., Xie, J. -X, Kupsch, A., Oertel, W. H., Morgenstern, R., Emilien, G. M., Maloteaux, J. M., Seghers, A., Charles, G., Erdmann, R., Högemann, D., Fichter, N., Lücking, C. H., Landwehrmeyer, G. B., Winter, T., Feuerstein, T. J., Fitzgeral, D., Anderson, M. C., Lawlor, B., Tipton, K. F., Frackowiak, R. S. J., Freo, U., Dam, M., Pizzolato, G., Merico, A., Ori, C., Sale, E., Battistin, L., Fritze, J., Froelich, L., Goetz, M., Gsell, W., Jellinger, K., Beckmann, H., Fünfgeld, E. W., Glinka, Y., Youdim, M. B. H., Götz, M. E., Breithaupt, W., Burger, R., Streifler, M., Simanyi, M., Müller, F., Danielczyk, W., Hirning, T., Sohlbach, M., Nafc, R., Sternadl, H., Winter, M., Nöth, U., Heim, C., Hartmann, J., Künig, G., Niedermeyer, B., Berger, W., Deckert, J., Abel, F., Heinsen, H., Senitz, D., Mayr, J., Ransmayr, G., Hartung, H. -P., Heils, A., Teufel, A., Petri, S., Seemann, M., Bengel, D., Degen, H. J., Lesch, K. P., Sontag, T., Heinen, F., Korinthenberg, R., Heiss, W. -D., Rüb, U., Gangus, B., Jungkunz, G., Bauer, M., Ulmar, G., Böcker, F., Schüler, M., Bethke, B., Lockemann, U., Hermans, E., Vanhoorde, P., Hesse, S., Hüll, M., Fiebich, B., Lieb, K., Strauss, S., Berger, M., Volk, B., Bauer, J., Iversen, L. L., Janetzky, B., Hauck, S., Jeanjean, A. P., Laterre, E. C., Bancher, C., Jost, W. H., Kalus, P., Kanner, B., Khrapova, E. V., Brusov, O. S., Knauber, J., Müller, W. E., Korczyn, A. D., Kornhuber, J., Parsons, C. G., Hartmann, S., Retz, W., Kamolz, S., Thome, J., Koutsilieri, E., Chen, T. -S., Kreutzberg, G. W., Krieglstein, J., Winkel, R., Danielcyk, S., Gerstner, A., Mattern, C., Häcker, R., Labunsky, D., Zhirnova, I., Komelkova, L., Popova, L., Avdiunina, I., Lakke, J. P. W. F., Lange, K. W., Steup, A., Tucha, O., Naumann, M., Lassmann, H., Leszek, J., Gasiorowski, K., Inglot, D., Lohse, M. J., Löschmann, P. -A., Eblen, F., Wüllner, U., Klockgether, T., Dichgans, J., Macrae, I. M., Mimmack, M. L., Emson, P., Norta, M., Borchert, H. -H., Medori, R., Chan, W. W., Heinemann, T., Melzacka, M., Kolasiewicz, W., Sieklucka, M., Jaros, T., Mesec, A., Šega, S., Kiauta, T., Moser, A., Vieregge, P., Siebecker, F., Münch, G., Schinzel, R., Michaelis, J., Cunningham, A., Da Prada, M., Borroni, E., Zürcher, G., Reiners, K., Neveu, P. J., Nitsch, R. M., Pavese, N., Lucetti, C., Rossi, G., Offen, D., Ziv, I., Stein, R., Barzilai, A., Hochman, A., Melamed, E., Ozawa, H., Hashimoto, E., Saito, T., Ymamoto, M., Takahata, N., Frölich, L., Paulus, W., Hermsteiner, E., Haug, B., Bandelow, B., Peckys, D., Gleichauf, O., Jackisch, R., Landwehrmeyer, B., Bloß, H. G., Plaschke, K., Müller, D., Hoyer, S., Avdyuna, L. A., Putzke, J., Spanagel, R., Tolle, T. R., Zieglgänsberger, W., Rabey, J. -M., Orlov, E., von Raison, F., Lehmann, K., Havemann-Reinecke, U., Butà, M., Federspiel, S., Maier, H., Abdel-mohsen, M., Abdel-moneim, M., Reynolds, G. P., Sardar, A. M., Eggett, C. J., Rosario, P., de la Morena, E., José Barro, M., Rossini, P. M., Roth, J., Růžička, E., Svobodová, I., Mečíř, P., Jech, R., Remeš, F., Kleinschroth, A., Schliebs, R., Roßner, S., Heider, M., Schubert, H., König, P., Schuttes, H., HaveIec, L., Schwartz, J. -C., Sendtner, M., Smith, A., Li, M., Griesbeck, O., Parsadanian, A., Holtmann, B., Carroll, P., Toyka, K. V., Thoenen, H., Sharkawy, A. A., Ibrahim, T. A., Pulkowski, U., Siesjö, B. K., Klessaschek, M., Sopper, S., Demuth, M., Dörries, R., Hemm, S., Stahl-Hennig, C., Brinkmann, R., ter Meulen, V., Sperk, G., Schwarzer, C., Stern, G., Storm, G., Strein, I., Struck, M., Stürenburg, H. J., Kunze, K., Svadovsky, A. I., Morgunov, K. V., Peresedov, V. V., Moshkin, A. V., Teherani, D. K., Baumer, A., Rösier, M., Rösler, M., Wiesbeck, G. A., Wodarz, N., Boning, J., Timerbaeva, S. L., Alekseeva, N. S., Toso, A., Barletta, D., Tuulik, V., Lossmann, E., Raja, A., Meister, A., Uitti, R. J., Rajput, A. H., Ahlskog, J. E., Offord, K. P., Schroeder, D. R., O'Brien, P. C., Vaglini, F., Fascetti, F., Pardini, C., Mancino, L., Velbinger, K., Hartmann, H., Eckert, A., Grüter, S., Behrens, S., Niemann, J., Guschelbauer, B., Lauk, M., Wissel, J., Poewe, W., Wurthman, C., Janzen, E. N. H., Goping, G., Adegemo, O. M., Gemma, A., Kuijpers, J., Pollard, H. B., Zielke, B., Ziemann, U., and Bruns, D.

Published
1995
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42. Exploration of the Genetic Architecture of Idiopathic Generalized Epilepsies

Author

Hempelmann, Anne, Taylor, Kirsten P., Heils, Armin, Lorenz, Susanne, PrudʼHomme, Jean-Francois, Nabbout, Rima, Dulac, Olivier, Rudolf, Gabrielle, Zara, Federico, Bianchi, Amedeo, Robinson, Robert, Mark Gardiner, R., Covanis, Athanasios, Lindhout, Dick, Stephani, Ulrich, Elger, Christian E., Weber, Yvonne G., Lerche, Holger, Nürnberg, Peter, Kron, Katherine L., Scheffer, Ingrid E., Mulley, John C., Berkovic, Samuel F., and Sander, Thomas

Published
2006

45. Association of anxiety-related traits with a polymorphism in the Serotonin transporter gene regulatory region

Author

Lesch, Klaus-Peter, Bengel, Dietmar, Heils, Armin, Sabol, Sue Z., Greenberg, Benjamin D., Petri, Susanne, Benjamin, Jonathan, Muller, Clemens R., Hamer, Dean, and Murphy, Dennis L.

Subjects
Personality -- Genetic aspects -- Research, Neuroses -- Genetic aspects -- Research, Anxiety -- Genetic aspects -- Research, Serotonin -- Research -- Genetic aspects, Science and technology, Genetic aspects, Research
Abstract

Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships., Anxiety-related traits are fundamental, enduring, and continuously distributed dimensions of normal human personality (1-3). Although twin studies have indicated that individual variation in measures of anxiety-related personality traits is 40 [...]

Published
1996

47. Exploration of a Putative Susceptibility Locus for Idiopathic Generalized Epilepsy on Chromosome 8p12

Author

Sander, Thomas, Windemuth, Christine, Schulz, Herbert, Saar, Kathrin, Gennaro, Elena, Riggio, Concetta, Bianchi, Amedeo, Zara, Federico, Rudolf, Gabrielle, Picard, Fabienne, Bulteau, Christine, Kaminska, Anna, Cieuta, Cécile, Prudʼhomme, Jean-François, Dulac, Olivier, Bate, Louise, Robinson, Robert, Gardiner, R. Mark, Covanis, Athanasios, de Haan, Gerrit-Jan, Janssen, Guus A. M. A. J., van Erp, M. Gerard, Boezeman, Eduard H. J. F., Lindhout, Dick, Heils, Armin, Nürnberg, Peter, and Janz, Diéter

Published
2003

50. Enzymatic Reactive Absorption and Distillation

Author

Matthias Wierschem, Andrzej Górak, Mathias Leimbrink, Mirko Skiborowski, Rene Heils, and Irina Smirnova

Subjects
Reaction rate, Solvent, chemistry.chemical_compound, chemistry, law, Scientific method, Absorption (electromagnetic radiation), Selectivity, Combinatorial chemistry, Distillation, Butyl butyrate, Catalysis, law.invention
Abstract

In this work, innovative concepts for reactive separation processes, such as reactive absorption and distillation, that make use of bio-based catalysts, in specific enzymes, are discussed. Enzymatic Reactive Absorption (ERA) and Distillation (ERD) offer potential for energy and investment savings or improved selectivity by exploiting enzyme merits like high enantioselectivity and high reaction rates at milder reaction conditions than chemical catalysts. Potential process equipment, application strategies to supply enzyme for ERA and ERD processes as well as suitable modeling and design approaches are presented. Despite the huge potential, addressing these issues is crucial in order to promote ERA and ERD as vital technologies for process intensification in bio-based industries. The application of the enzyme carbonic anhydrase in an ERA column with common MDEA-based solvent can drastically improve the absorption of CO2 by more than 9-fold. Furthermore, the production of butyl butyrate and enantiomerically pure (R)-1-phenylethyl acetate or (S)-2-pentanol were successfully demonstrated in an ERD column. These processes provided high conversion rates of the substrates and purities of the product stream at milder process conditions compared to conventional processes.

Published
2018

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