445 results on '"Zimmermann, Sabine"'
Search Results
202. Überlegungen zum Verhältnis ländlicher Bevölkerungen und Wald in Entwicklungsländern
- Author
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Irmann-Zimmermann, Sabine
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- 1989
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203. Two-dimensional NMR studies of the porcine muscle adenylate kinase
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Klaus, Werner, primary, Scharf, Michael, additional, Zimmermann, Sabine, additional, and Roesch, Paul, additional
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- 1988
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204. Secrets of the fungus-specific potassium channel TOK family.
- Author
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Houdinet, Gabriella, Guerrero-Galán, Carmen, Rose, Benjamin D., Garcia, Kevin, and Zimmermann, Sabine D.
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POTASSIUM channels , *TRANSMEMBRANE domains , *FILAMENTOUS fungi , *YEAST fungi , *BINDING sites - Abstract
The tandem-pore outward-rectifying potassium (K+) channel family (TOK) is found only in fungi. Therefore, a specific role in fungus physiology can be assumed. ScTOK1 was the first TOK channel characterized in Saccharomyces cerevisiae that displayed a unique structure: two pore domains and eight transmembrane domains per subunit. ScTOK1 induces mainly outward K+ currents upon membrane depolarization, and is highly regulated. The gating model of TOK channels has evolved over the years and involves external and internal K+ concentration, potential binding sites, and membrane potential. TOK channels have also been found recently in filamentous fungi, and light has been shed on their potential role in beneficial and pathogenic interactions with host organisms. Several families of potassium (K+) channels are found in membranes of all eukaryotes, underlining the importance of K+ uptake and redistribution within and between cells and organs. Among them, TOK (tandem-pore outward-rectifying K+) channels consist of eight transmembrane domains and two pore domains per subunit organized in dimers. These channels were originally studied in yeast, but recent identifications and characterizations in filamentous fungi shed new light on this fungus-specific K+ channel family. Although their actual function in vivo is often puzzling, recent works indicate a role in cellular K+ homeostasis and even suggest a role in plant–fungus symbioses. This review aims at synthesizing the current knowledge on fungal TOK channels and discussing their potential role in yeasts and filamentous fungi. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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205. Effects of endothelin-1 in the isolated heart in ischemia/reperfusion and hypoxia/reoxygenation injury
- Author
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Neubauer, Stefan, Zimmermann, Sabine, Hirsch, Annette, Pulzer, Ferdinand, Tian, Roug, Bauer, Wolfgang, Bauer, Barbara, and Ertl, Georg
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- 1991
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206. Association of plant K +in channels is mediated by conserved C-termini and does not affect subunit assembly
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Ehrhardt, Thomas, Zimmermann, Sabine, and Müller-Röber, Bernd
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- 1997
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207. Time course of anger and other emotions in women with borderline personality disorder: A preliminary study
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Jacob, Gitta A., Guenzler, Cindy, Zimmermann, Sabine, Scheel, Corinna N., Rüsch, Nicolas, Leonhart, Rainer, Nerb, Josef, and Lieb, Klaus
- Subjects
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ANGER , *EMOTIONS , *PERSONALITY disorders , *PATHOLOGICAL psychology - Abstract
Abstract: Borderline personality disorder (BPD) is characterized by emotional dysregulation including strong emotional reactions to emotional stimuli and a slow return to baseline emotions. Difficulties controlling anger are particularly prominent in BPD. To experimentally test emotional dysregulation with a special focus on anger, we investigated whether a standardized anger induction by a short story caused stronger and prolonged anger reactions in women with BPD (n=27) as compared to female healthy controls (n=26) and whether other emotions were affected by the anger induction. Although the anger reaction was not stronger in the BPD group, it was significantly prolonged. The BPD group showed also stronger negative emotions over the whole experiment. The study is the first to demonstrate prolonged anger reactions in BPD patients in an experimental setting. [Copyright &y& Elsevier]
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- 2008
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208. Molecular mechanisms and regulation of plant ion channels.
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Czempinski, Katrin, Gaedeke, Nicola, Zimmermann, Sabine, and Müller-Röber, Bernd
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ARABIDOPSIS , *XENOPUS , *CELLS , *ION channels , *ELECTROPHYSIOLOGY , *PHARMACOLOGY - Abstract
Plant ion channel activities are rapidly modulated in response to several environmental and endogenous stimuli. Electrophysiological as well as pharmacological studies provide strong evidence that ion channels are essential for the induction of specific cellular responses and that they are themselves subject to regulation by a variety of cellular factors. Genes and cDNAs of several plant ion channels have been identified in recent years giving access to molecular mechanisms of such regulatory processes. Cloned inwardly rectifying potassium channels have been investigated in various heterologous expression systems. Two other ion channel classes, namely members of the 'two-pore' K+ channel family as well as of the anion-conducting chloride channel (CIC) family, have been cloned, but a direct link to corresponding plasma membrane or endomembrane ion channel conductances has not been demonstrated yet. Analysis of cellular expression patterns of plant ion channel genes in combination with transgenic approaches now gives access to a detailed ex planta/in planta correlation of channel function, as has recently been demonstrated for proteins of the Kin+ channel family. This review summarizes current knowledge on molecular structures and some features of structure-function relationships of plant ion channels. [ABSTRACT FROM PUBLISHER]
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- 1999
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209. Datamining and functional environmental genomics reassess the phylogenetics and functional diversity of fungal monosaccharide transporters.
- Author
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Barbi, Florian, Vallon, Laurent, Guerrero-Galán, Carmen, Zimmermann, Sabine D., Melayah, Delphine, Abrouk, Danis, Doré, Jeanne, Lemaire, Marc, Fraissinet-Tachet, Laurence, Luis, Patricia, and Marmeisse, Roland
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FUNCTIONAL genomics , *MONOSACCHARIDES , *FUNGAL proteins , *ANTISENSE DNA , *YEAST fungi , *PHYLOGENY , *XENOPUS laevis , *GALACTOSE - Abstract
Sugar transporters are essential components of carbon metabolism and have been extensively studied to control sugar uptake by yeasts and filamentous fungi used in fermentation processes. Based on published information on characterized fungal sugar porters, we show that this protein family encompasses phylogenetically distinct clades. While several clades encompass transporters that seemingly specialized on specific "sugar-related" molecules (e.g., myo-inositol, charged sugar analogs), others include mostly either mono- or di/oligosaccharide low-specificity transporters. To address the issue of substrate specificity of sugar transporters, that protein primary sequences do not fully reveal, we screened "multi-species" soil eukaryotic cDNA libraries for mannose transporters, a sugar that had never been used to select transporters. We obtained 19 environmental transporters, mostly from Basidiomycota and Ascomycota. Among them, one belonged to the unusual "Fucose H+ Symporter" family, which is only known in Fungi for a rhamnose transporter in Aspergillus niger. Functional analysis of the 19 transporters by expression in yeast and for two of them in Xenopus laevis oocytes for electrophysiological measurements indicated that most of them showed a preference for d-mannose over other tested d-C6 (glucose, fructose, galactose) or d-C5 (xylose) sugars. For the several glucose and fructose-negative transporters, growth of the corresponding recombinant yeast strains was prevented on mannose in the presence of one of these sugars that may act by competition for the binding site. Our results highlight the potential of environmental genomics to figure out the functional diversity of key fungal protein families and that can be explored in a context of biotechnology. Key points: • Most fungal sugar transporters accept several sugars as substrates. • Transporters, belonging to 2 protein families, were isolated from soil cDNA libraries. • Environmental transporters featured novel substrate specificities. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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210. Chapter Three - The ectomycorrhizal contribution to tree nutrition.
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Becquer, Adeline, Guerrero-Galán, Carmen, Eibensteiner, Janice L., Houdinet, Gabriella, Bücking, Heike, Zimmermann, Sabine D., and Garcia, Kevin
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BOTANICAL periodicals , *ECTOMYCORRHIZAS , *TREES , *NUTRITION - Abstract
Trees can be associated with dozens of fungi helping them to acquire resources from forest soils. The most widespread mutualistic association in boreal and temperate forests is the ectomycorrhizal symbiosis. This symbiosis involves mushroom-forming fungi of basidiomycota, ascomycota, and some zygomycota clades and the roots of woody plant species, including oaks, poplars or pines. Although the impact of this association on ecosystem production and tree nutrition is investigated for about a century, our understanding on the molecular mechanisms that control water and nutrient fluxes between plant and fungal partners is still limited. Here, we review the recent knowledge on the ectomycorrhizal contribution to tree nutrition. We specifically highlight the molecular mechanisms driving the acquisition, translocation and release of water and nutrients in ectomycorrhizal systems. We particularly focus on the transport of macronutrients, including nitrogen, phosphorus, potassium, sulphur and calcium, micronutrients, and water by the symbiotic partner. We also provide background on the evolution, diversity, and importance of this symbiosis, identify knowledge gaps, and propose future research directions. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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211. Chapter Ten - The Role of Plant Transporters in Mycorrhizal Symbioses.
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Guerrero-Galán, Carmen, Houdinet, Gabriella, Calvo-Polanco, Monica, Bonaldi, Katia E., Garcia, Kevin, and Zimmermann, Sabine Dagmar
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BOTANICAL periodicals , *BIOLOGICAL transport , *MYCORRHIZAL plants , *PLANT nutrition , *PLANTS - Abstract
Membrane transport systems are crucial elements for plant nutrition and development as they play a key role in the absorption of mineral nutrients and water at the root level but also in the translocation within the plant. Moreover, membrane transport is involved in signalling and communication e.g. to adapt and interact with the environment. Most plants live in tight contact with beneficial soil microbes, such as bacteria and mycorrhizal fungi, which contribute to plant nutrition in part through modulation of the expression and functioning of plant transporter systems, as ion channels and transporters. In addition, mycorrhizal fungi largely increase the absorption surface of roots thereby promoting plant's access to soil resources as minerals and water. In turn, plants "reward" mycorrhizal fungi with sugars and/or lipids. This "fair trade" requires specific communication and a series of exchanges between the two symbiotic partners enabled by the adaptability and plasticity of their transporters. Here, we summarize recent advances allowing molecular insight in the impact of mycorrhizal symbiosis on the plant "transportome". We highlight results obtained in ecto- and endomycorrhizal associations for plant transporters involved in the absorption of mineral nutrients and water released by the fungus at the symbiotic interface, and molecular players responsible for carbon and lipid nutrition of the fungal partner. We focus also on plant membrane transport systems implicated in early communication between plant and fungal partners. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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212. The Arabidopsis root stele transporter NPF2.3 contributes to nitrate translocation to shoots under salt stress.
- Author
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Taochy, Christelle, Gaillard, Isabelle, Ipotesi, Emilie, Oomen, Ronald, Leonhardt, Nathalie, Zimmermann, Sabine, Peltier, Jean‐Benoît, Szponarski, Wojciech, Simonneau, Thierry, Sentenac, Hervé, Gibrat, Rémy, and Boyer, Jean‐Christophe
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ARABIDOPSIS , *PLANT roots , *CHROMOSOMAL translocation , *NITRATES , *PLANT shoots - Abstract
In most plants [ABSTRACT FROM AUTHOR]
- Published
- 2015
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213. Plant potassium nutrition in ectomycorrhizal symbiosis: properties and roles of the three fungal TOK potassium channels in Hebeloma cylindrosporum
- Author
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Geneviève Conejero, Gabriella Houdinet, Isabelle Gaillard, Hervé Sentenac, Carmen Guerrero-Galán, Sabine Zimmermann, Kevin Garcia, Amandine Delteil, Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie et physiologie des plantes, Institut National de la Recherche Agronomique (INRA), Biology and Microbiology Department, South Dakota State University (SDSTATE), Plateforme Histocytologie et Imagerie Cellulaire Végétale, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Zimmermann, Sabine, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
- Subjects
0106 biological sciences ,0301 basic medicine ,Potassium Channels ,Saccharomyces cerevisiae ,Fungus ,maritime pine ,absorption du potassium ,champignon mycorhizien ,01 natural sciences ,Microbiology ,nutrition minérale ,Ectosymbiosis ,03 medical and health sciences ,Symbiosis ,Mycorrhizae ,Botany ,Hebeloma ,ion potassium ,[SDV.BV]Life Sciences [q-bio]/Vegetal Biology ,Axenic ,Ecology, Evolution, Behavior and Systematics ,Minerals ,Vegetal Biology ,pinus pinaster ,shaker potassium channel ,biology ,fungi ,Biological Transport ,15. Life on land ,Pinus ,biology.organism_classification ,Yeast ,Complementation ,hebeloma cylindrosporum ,030104 developmental biology ,Seedlings ,Potassium ,Pinus pinaster ,canaux potassiques shaker ,Plant nutrition ,Biologie végétale ,010606 plant biology & botany - Abstract
Ectomycorrhizal fungi play an essential role in the ecology of boreal and temperate forests through the improvement of tree mineral nutrition. Potassium (K+ ) is an essential nutrient for plants and is needed in high amounts. We recently demonstrated that the ectomycorrhizal fungus Hebeloma cylindrosporum improves the K+ nutrition of Pinus pinaster under shortage conditions. Part of the transport systems involved in K+ uptake by the fungus has been deciphered, while the molecular players responsible for the transfer of this cation towards the plant remain totally unknown. Analysis of the genome of H. cylindrosporum revealed the presence of three putative tandem-pore outward-rectifying K+ (TOK) channels that could contribute to this transfer. Here, we report the functional characterization of these three channels through two-electrode voltage-clamp experiments in oocytes and yeast complementation assays. The expression pattern and physiological role of these channels were analysed in symbiotic interaction with P. pinaster. Pine seedlings colonized by fungal transformants overexpressing two of them displayed a larger accumulation of K+ in shoots. This study revealed that TOK channels have distinctive properties and functions in axenic and symbiotic conditions and suggested that HcTOK2.2 is implicated in the symbiotic transfer of K+ from the fungus towards the plant.
- Published
- 2018
214. The effects of emotion regulation on the desire to overeat in restrained eaters
- Author
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Svaldi, Jennifer, Tuschen-Caffier, Brunna, Lackner, Helmut K., Zimmermann, Sabine, and Naumann, Eva
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EMOTIONS , *HYPERPHAGIA , *PARASYMPATHETIC nervous system , *SYMPATHETIC nervous system , *PSYCHOPHYSIOLOGY , *MATHEMATICAL models - Abstract
Abstract: The aim of the present study was to test whether emotion regulation (ER) strategies are underlying processes in the link between negative emotions and the desire to overeat (DTE) in high restrained eaters (HR). Forty-eight female HR and 46 female low restrained eaters (LR) watched three sadness inducing film clips. Thereby, participants were randomly assigned to and trained in one of three conditions while watching the first two clips: to suppress upcoming emotions, to accept upcoming emotions or to reappraise the situation. After that, they participated in an experiment in which the learned ER strategy was implemented while watching the third sadness inducing film clip. DTE and sadness were assessed prior to and at the end of each clip. Additionally, physiological measures of the sympathetic and parasympathetic branch were obtained. In the HR group emotion acceptance and suppression lead to a significant increase of the DTE from baseline to post-film, while there was no change in DTE in the reappraisal condition. However, psychophysiological measures were not moderated by ER strategies. The results are discussed in terms of the limited resource model. [Copyright &y& Elsevier]
- Published
- 2012
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215. Peptide uptake in the ectomycorrhizal fungus Hebeloma cylindrosporum: characterization of two di- and tripeptide transporters (HcPTR2A and B).
- Author
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Benjdia, Mariam, Rikirsch, Enno, Müller, Tobias, Morel, Mélanie, Corratgé, Claire, Zimmermann, Sabine, Chalot, Michel, Frommer, Wolf B., and Wipf, Daniel
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ECTOMYCORRHIZAL fungi , *HEBELOMA , *PARASITIC plants , *PLANT growth , *YEAST fungi , *PEPTIDES - Abstract
• Constraints on plant growth imposed by low availability of nitrogen are a characteristic feature of ecosystems dominated by ectomycorrhizal plants. Ectomycorrhizal fungi play a key role in the N nutrition of plants, allowing their host plants to access decomposition products of dead plant and animal materials. Ectomycorrhizal plants are thus able to compensate for the low availability of inorganic N in forest ecosystems. • The capacity to take up peptides, as well as the transport mechanisms involved, were analysed in the ectomycorrhizal fungus Hebeloma cylindrosporum. • The present study demonstrated that H. cylindrosporum mycelium was able to take up di- and tripeptides and use them as sole N source. Two peptide transporters (HcPTR2A and B) were isolated by yeast functional complementation using an H. cylindrosporum cDNA library, and were shown to mediate dipeptide uptake. • Uptake capacities and expression regulation of both genes were analysed, indicating that HcPTR2A was involved in the high-efficiency peptide uptake under conditions of limited N availability, whereas HcPTR2B was expressed constitutively. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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216. Identification and characterization of plant transporters using heterologous expression systems.
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Dreyer, Ingo, Horeau, Christèle, Lemaillet, Guy, Zimmermann, Sabine, Bush, Daniel R., Rodríguez-Navarro, Alonso, Schachtman, Daniel P., Spalding, Edgar P., Sentenac, Hervé, and Gaber, Richard F.
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PLANT membranes , *CARRIER proteins , *PLANT physiology , *ATMOSPHERE , *PHOTOSYNTHESIS - Abstract
In recent years major progress has been achieved in the understanding of transport processes in higher plants. The boom in the field of molecular plant physiology led to the identification and characterization of membrane transporters with transport activities for potassium, calcium, sugars, nitrate, ammonium, sulphate, phosphate, amino acids, peptides, and metal ions. Such progress was hardly feasible without heterologous expression of the isolated transport proteins. This review summarizes the different approaches in characterizing plant membrane transporters using heterologous expression systems. By presenting concrete examples, it outlines different cloning strategies, displays the methods used for (i) expression of transport proteins and detection of their function, (ii) biochemical analyses, (iii) explorations of the structure-function relationship through mutational analysis, and concludes with a discussion about the physiological relevance of the analyses in heterologous expression systems. [ABSTRACT FROM PUBLISHER]
- Published
- 1999
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217. Engineered HCMV-infected APCs enable the identification of new immunodominant HLA-restricted epitopes of anti-HCMV T-cell immunity.
- Author
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Santamorena MM, Tischer-Zimmermann S, Bonifacius A, Mireisz CN, Costa B, Khan F, Kulkarni U, Lauruschkat CD, Sampaio KL, Stripecke R, Blasczyk R, Maecker-Kolhoff B, Kraus S, Schlosser A, Cicin-Sain L, Kalinke U, and Eiz-Vesper B
- Subjects
- Humans, HLA-A11 Antigen immunology, HLA-A11 Antigen genetics, Fibroblasts immunology, Fibroblasts virology, Antigen-Presenting Cells immunology, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, Immunodominant Epitopes immunology, Dendritic Cells immunology, Epitopes, T-Lymphocyte immunology
- Abstract
Complications due to HCMV infection or reactivation remain a challenging clinical problem in immunocompromised patients, mainly due to insufficient or absent T-cell functionality. Knowledge of viral targets is crucial to improve monitoring of high-risk patients and optimise antiviral T-cell therapy. To expand the epitope spectrum, genetically-engineered dendritic cells (DCs) and fibroblasts were designed to secrete soluble (s)HLA-A*11:01 and infected with an HCMV mutant lacking immune evasion molecules (US2-6 + 11). More than 700 HLA-A*11:01-restricted epitopes, including more than 50 epitopes derived from a broad range of HCMV open-reading-frames (ORFs) were identified by mass spectrometry and screened for HLA-A*11:01-binding using established prediction tools. The immunogenicity of the 24 highest scoring new candidates was evaluated in vitro in healthy HLA-A*11:01
+ /HCMV+ donors. Thus, four subdominant epitopes and one immunodominant epitope, derived from the anti-apoptotic protein UL36 and ORFL101C (A11SAL ), were identified. Their HLA-A*11:01 complex stability was verified in vitro. In depth analyses revealed highly proliferative and cytotoxic memory T-cell responses against A11SAL , with T-cell responses comparable to the immunodominant HLA-A*02:01-restricted HCMVpp65NLV epitope. A11SAL -specific T cells were also detectable in vivo in immunosuppressed transplant patients and shown to be effective in an in vitro HCMV-infection model, suggesting their crucial role in inhibiting viral replication and improvement of patient's outcome. The developed in vitro pipeline is the first to utilise genetically-engineered DCs to identify naturally presented immunodominant HCMV-derived epitopes. It therefore offers advantages over in silico predictions, is transferable to other HLA alleles, and will significantly expand the repertoire of viral targets to improve therapeutic options., (© 2024 The Author(s). HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)- Published
- 2024
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218. Combined treatment with allogeneic Epstein-Barr- and human polyomavirus 1 specific T-cells in progressive multifocal leukoencephalopathy and EBV infection: a case report.
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Nay S, Möhn N, Grote-Levi L, Bonifacius A, Saßmann ML, Karacondi K, Tischer-Zimmermann S, Pöter H, Mahmoudi N, Wattjes MP, Maecker-Kolhoff B, Höglinger G, Eiz-Vesper B, and Skripuletz T
- Abstract
Opportunistic viral infections in individuals with severe immunodeficiency can lead to fatal conditions such as progressive multifocal leukoencephalopathy (PML), for which treatment options are limited. These infections pose significant risks, especially when co-infections with other viruses occur. We describe a combined therapy approach using directly isolated allogeneic Human Polyomavirus 1 (also known as BKV) and Epstein-Barr virus (EBV) specific cytotoxic T-cells for the treatment of PML in conjunction with identified EBV in the cerebrospinal fluid (CSF) of a male patient infected with human immunodeficiency virus (HIV). A 53-year-old HIV-positive male, recently diagnosed with PML, presented with rapidly worsening symptoms, including ataxia, tetraparesis, dysarthria, and dysphagia, leading to respiratory failure. The patient developed PML even after commencing highly active antiretroviral therapy (HAART) 3 months prior. Brain magnetic resonance imaging (MRI) revealed multifocal demyelination lesions involving the posterior fossa and right thalamus suggestive of PML. In addition to the detection of human polyomavirus 2 (also known as JCV), analysis of CSF showed positive results for EBV deoxyribonucleic acid (DNA). His neurological condition markedly deteriorated over the following 2 months. Based on MRI, there was no evidence of Immune Reconstitution Inflammatory Syndrome contributing to this decline. The patient did not have endogenous virus-specific T-cells. We initiated an allogeneic, partially human leukocyte antigen-matched transfer of EBV and utilizing the cross-reactivity between BKV and JCV-BKV specific T-cells. This intervention led to notable neurological improvement and partial resolution of the MRI lesions within 6 weeks. Our case of a patient with acquired immune deficiency syndrome demonstrates that PML and concurrent EBV co-infection can still occur despite undergoing HAART treatment. This innovative experimental therapy, involving a combination of virus-specific T-cells, was demonstrated to be an effective treatment option in this patient., (© The Author(s), 2024.)
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- 2024
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219. Editorial: Mechanisms and practices for the management of plant-soil biota interaction.
- Author
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Saia S, Radicetti E, Pawlowski K, Zimmermann SD, and Genre A
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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- 2024
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220. The ectomycorrhizal fungus Paxillus ammoniavirescens influences the effects of salinity on loblolly pine in response to potassium availability.
- Author
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Rose BD, Dellinger MA, Larmour CP, Polishook MI, Higuita-Aguirre MI, Dutta S, Cook RL, Zimmermann SD, and Garcia K
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- Pinus taeda genetics, Salinity, Potassium, Mycorrhizae, Basidiomycota
- Abstract
Salinity is an increasing problem in coastal areas affected by saltwater intrusion, with deleterious effects on tree health and forest growth. Ectomycorrhizal (ECM) fungi may improve the salinity tolerance of host trees, but the impact of external potassium (K
+ ) availability on these effects is still unclear. Here, we performed several experiments with the ECM fungus Paxillus ammoniavirescens and loblolly pine (Pinus taeda L.) in axenic and symbiotic conditions at limited or sufficient K+ and increasing sodium (Na+ ) concentrations. Growth rate, biomass, nutrient content, and K+ transporter expression levels were recorded for the fungus, and the colonization rate, root development parameters, biomass, and shoot nutrient accumulation were determined for mycorrhizal and non-mycorrhizal plants. P. ammoniavirescens was tolerant to high salinity, although growth and nutrient concentrations varied with K+ availability and increasing Na+ exposure. While loblolly pine root growth and development decreased with increasing salinity, ECM colonization was unaffected by pine response to salinity. The mycorrhizal influence on loblolly pine salinity response was strongly dependent on external K+ availability. This study reveals that P. ammoniavirescens can reduce Na+ accumulation of salt-exposed loblolly pine, but this effect depends on external K+ availability., (© 2024 The Authors. Environmental Microbiology published by John Wiley & Sons Ltd.)- Published
- 2024
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221. Identification of novel canonical and cryptic HCMV-specific T-cell epitopes for HLA-A∗03 and HLA-B∗15 via peptide-PRISM.
- Author
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Rein AF, Lauruschkat CD, Muchsin I, Köchel C, Tischer-Zimmermann S, Bauersfeld L, Nelde A, Lübke M, Prusty BK, Schlosser A, Halenius A, Eiz-Vesper B, Dölken L, Grigoleit GU, Einsele H, Erhard F, and Kraus S
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- Humans, Peptides, HLA-B Antigens, HLA-A Antigens, Cytomegalovirus, Epitopes, T-Lymphocyte
- Abstract
Abstract: Human cytomegalovirus (HCMV) reactivation poses a substantial risk to patients receiving tranplants. Effective risk stratification and vaccine development is hampered by a lack of HCMV-derived immunogenic peptides in patients with common HLA-A∗03:01 and HLA-B∗15:01 haplotypes. This study aimed to discover novel HCMV immunogenic peptides for these haplotypes by combining ribosome sequencing (Ribo-seq) and mass spectrometry with state-of-the-art computational tools, Peptide-PRISM and Probabilistic Inference of Codon Activities by an EM Algorithm. Furthermore, using machine learning, an algorithm was developed to predict immunogenicity based on translational activity, binding affinity, and peptide localization within small open reading frames to identify the most promising peptides for in vitro validation. Immunogenicity of these peptides was subsequently tested by analyzing peptide-specific T-cell responses of HCMV-seropositive and -seronegative healthy donors as well as patients with transplants. This resulted in the direct identification of 3 canonical and 1 cryptic HLA-A∗03-restricted immunogenic peptides as well as 5 canonical and 1 cryptic HLA-B∗15-restricted immunogenic peptide, with a specific interferon gamma-positive (IFN-γ+)/CD8+ T-cell response of ≥0.02%. High T-cell responses were detected against 2 HLA-A∗03-restricted and 3 HLA-B∗15-restricted canonical peptides with frequencies of up to 8.77% IFN-γ+/CD8+ T cells in patients after allogeneic stem cell transplantation. Therefore, our comprehensive strategy establishes a framework for efficient identification of novel immunogenic peptides from both existing and novel Ribo-seq data sets., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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222. Editorial: Importance of root symbiomes for plant nutrition: new insights, perspectives and future challenges, volume II.
- Author
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Das D, Kafle A, Ho-Plágaro T, Zimmermann SD, Bücking H, and Garcia K
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
- Published
- 2023
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223. Adoptive Allogeneic T-Cell Therapy Improves the Clinical Outcome of JC Virus Granule Cell Neuronopathy: A Case Report.
- Author
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Grote-Levi L, Möhn N, Bonifacius A, Tischer-Zimmermann S, Schweitzer F, Mahmoudi N, Silling S, Warnke C, Maecker-Kolhoff B, Wattjes MP, Eiz-Vesper B, Höglinger GU, and Skripuletz T
- Subjects
- Humans, Cerebellum, Atrophy, Cell- and Tissue-Based Therapy, JC Virus, Hematopoietic Stem Cell Transplantation
- Abstract
Objectives: JC virus granule cell neuronopathy is a potentially fatal otherwise highly disabling disease without an approved therapeutic option. This case report presents the positive record to T-cell therapy in JC virus granule cell neuronopathy., Methods: The patient represented with subacute cerebellar symptoms. Diagnosis of JC virus granule cell neuronopathy was made because of infratentorially accentuated brain volume atrophy shown by brain MRI and the detection of JC virus DNA in the CSF., Results: Six doses of virus-specific T cells were administered. Within 12 months after therapy initiation, the patient showed clear clinical benefit with improvement of symptoms, and JC viral DNA load significantly declined., Discussion: We present the case report of a positive response to T-cell therapy in JC virus granule cell neuronopathy, leading to an improvement of symptoms., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
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- 2023
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224. Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors.
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Bonifacius A, Lamottke B, Tischer-Zimmermann S, Schultze-Florey R, Goudeva L, Heuft HG, Arseniev L, Beier R, Beutel G, Cario G, Fröhlich B, Greil J, Hansmann L, Hasenkamp J, Höfs M, Hundsdoerfer P, Jost E, Kafa K, Kriege O, Kröger N, Mathas S, Meisel R, Nathrath M, Putkonen M, Ravens S, Reinhardt HC, Sala E, Sauer MG, Schmitt C, Schroers R, Steckel NK, Trappe RU, Verbeek M, Wolff D, Blasczyk R, Eiz-Vesper B, and Maecker-Kolhoff B
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- Humans, Herpesvirus 4, Human, Retrospective Studies, T-Lymphocytes, Cytotoxic, Unrelated Donors, Epstein-Barr Virus Infections, Immunotherapy, Adoptive methods
- Abstract
BACKGROUNDAdoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications.METHODSWe provide results of a personalized T cell manufacturing program evaluating donor, patient, T cell product, and outcome data. Patient-tailored clinical-grade EBV-specific cytotoxic T lymphocyte (EBV-CTL) products from stem cell donors (SCDs), related third-party donors (TPDs), or unrelated TPDs from the allogeneic T cell donor registry (alloCELL) at Hannover Medical School were manufactured by immunomagnetic selection using a CliniMACS Plus or Prodigy device and the EBV PepTivators EBNA-1 and Select. Consecutive manufacturing processes were evaluated, and patient outcome and side effects were retrieved by retrospective chart analysis.RESULTSForty clinical-grade EBV-CTL products from SCDs, related TPDs, or unrelated TPDs were generated for 37 patients with refractory EBV infections or EBV-associated malignancies with and without a history of transplantation, within 5 days (median) after donor identification. Thirty-four patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to a complete response in 20 of 29 patients who were evaluated for clinical response. No infusion-related toxicity was reported. EBV-specific T cells in patients' blood were detectable in 16 of 18 monitored patients (89%) after transfer, and their presence correlated with clinical response.CONCLUSIONPersonalized clinical-grade manufacture of EBV-CTL products via immunomagnetic selection from SCDs, related TPDs, or unrelated TPDs in a timely manner is feasible. Overall, EBV-CTLs were clinically effective and well tolerated. Our data suggest EBV-CTL transfer as a promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT, as well as patients with preexisting organ dysfunction.TRIAL REGISTRATIONNot applicable.FUNDINGThis study was funded in part by the German Research Foundation (DFG, 158989968/SFB 900), the Deutsche Kinderkrebsstiftung (DKS 2013.09), Wilhelm-Sander-Stiftung (reference 2015.097.1), Ellen-Schmidt-Program of Hannover Medical School, and German Federal Ministry of Education and Research (reference 01EO0802).
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- 2023
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225. Overexpression of the HcPT1.1 transporter in Hebeloma cylindrosporum alters the phosphorus accumulation of Pinus pinaster and the distribution of HcPT2 in ectomycorrhizae.
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Amenc L, Becquer A, Trives-Segura C, Zimmermann SD, Garcia K, and Plassard C
- Abstract
Ectomycorrhizal (ECM) fungi are associated with the roots of woody plants in temperate and boreal forests and help them to acquire water and nutrients, particularly phosphorus (P). However, the molecular mechanisms responsible for the transfer of P from the fungus to the plant in ectomycorrhizae are still poorly understood. In the model association between the ECM fungus Hebeloma cylindrosporum and its host plant Pinus pinaster , we have shown that the fungus, which possesses three H+:Pi symporters (HcPT1.1, HcPT1.2 and HcPT2), expresses mainly HcPT1.1 and HcPT2 in the extraradical and intraradical hyphae of ectomycorrhizae to transport P from the soil to colonized roots. The present study focuses on the role of the HcPT1.1 protein in plant P nutrition, in function of P availability. We artificially overexpressed this P transporter by fungal Agrotransformation and investigated the effect of the different lines, wild-type and transformed ones, on plant P accumulation, the distribution of HcPT1.1 and HcPT2 proteins in ectomycorrhizae by immunolocalization, and 32P efflux in an experimental system mimicking intraradical hyphae. Surprisingly, we showed that plants interacting with transgenic fungal lines overexpressing HcPT1.1 did not accumulate more P in their shoots than plants colonized with the control ones. Although the overexpression of HcPT1.1 did not affect the expression levels of the other two P transporters in pure cultures, it induced a strong reduction in HcPT2 proteins in ectomycorrhizae, particularly in intraradical hyphae, but still improved the P status of host plant shoots compared with non-mycorrhizal plants. Finally, 32P efflux from hyphae was higher in lines overexpressing HcPT1.1 than in the control ones. These results suggest that a tight regulation and/or a functional redundancy between the H+:Pi symporters of H. cylindrosporum might exist to ensure a sustainable P delivery to P. pinaster roots ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Amenc, Becquer, Trives-Segura, Zimmermann, Garcia and Plassard.)
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- 2023
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226. Adenoviral Penton and Hexon Proteins Are Equivalent Immunogenic Targets of Virus-Specific T Cells after Hematopoietic Stem Cell Transplantation in Children.
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Wintering A, Tischer-Zimmermann S, Schultze-Florey R, Beier R, Sauer M, Blasczyk R, Heim A, Eiz-Vesper B, and Maecker-Kolhoff B
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- Humans, Child, Capsid Proteins, T-Lymphocytes, Adenoviridae, Antiviral Agents, Hematopoietic Stem Cell Transplantation adverse effects, Adenoviruses, Human, Adenovirus Infections, Human epidemiology, Adenovirus Infections, Human etiology
- Abstract
Human adenovirus (HAdV) infection is a serious complication that can lead to significant morbidity and mortality, especially in immunocompromised pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Control and elimination of HAdV requires the presence of the respective antiviral T cells, and adoptive transfer of virus-specific T cells has become an important new treatment option for patients refractory to antiviral treatment. Although the adenoviral capsid protein hexon is known to be a major immunodominant T cell target across HAdV species, up to 30% of HAdV-seropositive donors show no T cell responses to the overlapping peptide pool spanning the entire protein. Our group recently verified the capsid protein penton as a second immunodominant target in HAdV infection. Here we aimed to investigate the prevalence of both penton-specific and hexon-specific HAdV T cells and their impact in virus control after HSCT. We analyzed the prevalence and characteristics of HAdV-specific T cells in 33 consecutive pediatric patients with HAdV reactivation following allogeneic HSCT and correlated them with viral load analysis. Our study demonstrates that penton is an important immunodominant target antigen of HAdV reactivation/ infection after HSCT in most patients. We demonstrate that in the majority of patients, both penton- and hexon-specific T cells appear at similar time intervals after transplantation. Despite the prevalence for either hexon-specific or penton-specific T cells in individual patients, we were unable to attribute the predominance to specific HLA types or HAdV serotypes. The occurrence of HAdV-specific T cells was closely linked to viral control, arguing for immune monitoring strategies to tailor antiviral treatment and adoptive T cell therapy., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2023
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227. Epigenetic control is involved in molecular dialogue in plant-microbe symbiosis.
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Zimmermann SD and Gaillard I
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- Symbiosis, Plant Roots, Epigenomics, Epigenesis, Genetic, Mycorrhizae, Laccaria
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- 2023
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228. Rapid and sustained T cell-based immunotherapy against invasive fungal disease via a combined two step procedure.
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Tischer-Zimmermann S, Salzer E, Bitencourt T, Frank N, Hoffmann-Freimüller C, Stemberger J, Maecker-Kolhoff B, Blasczyk R, Witt V, Fritsch G, Paster W, Lion T, Eiz-Vesper B, and Geyeregger R
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- Aspergillus fumigatus, T-Lymphocytes, Helper-Inducer, Immunotherapy, Interferon-gamma, CD8-Positive T-Lymphocytes, Aspergillosis therapy
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Introduction: Aspergillus fumigatus (Asp) infections constitute a major cause of morbidity and mortality in patients following allogeneic hematopoietic stem cell transplantation (HSCT). In the context of insufficient host immunity, antifungal drugs show only limited efficacy. Faster and increased T-cell reconstitution correlated with a favorable outcome and a cell-based therapy approach strongly indicated successful clearance of fungal infections. Nevertheless, complex and cost- or time-intensive protocols hampered their implementation into clinical application., Methods: To facilitate the clinical-scale manufacturing process of Aspergillus fumigatus -specific T cells (ATCs) and to enable immediate (within 24 hours) and sustained (12 days later) treatment of patients with invasive aspergillosis (IA), we adapted and combined two complementary good manufacturing practice (GMP)-compliant approaches, i) the direct magnetic enrichment of Interferon-gamma (IFN-γ) secreting ATCs using the small-scale Cytokine Secretion Assay (CSA) and ii) a short-term in vitro T-cell culture expansion (STE), respectively. We further compared stimulation with two standardized and commercially available products: Asp-lysate and a pool of overlapping peptides derived from different Asp-proteins (PepMix)., Results: For the fast CSA-based approach we detected IFN-γ
+ ATCs after Asp-lysate- as well as PepMix-stimulation but with a significantly higher enrichment efficiency for stimulation with the Asp-lysate when compared to the PepMix. In contrast, the STE approach resulted in comparably high ATC expansion rates by using Asp-lysate or PepMix. Independent of the stimulus, predominantly CD4+ helper T cells with a central-memory phenotype were expanded while CD8+ T cells mainly showed an effector-memory phenotype. ATCs were highly functional and cytotoxic as determined by secretion of granzyme-B and IFN-γ., Discussion: For patients with IA, the immediate adoptive transfer of IFN-γ+ ATCs followed by the administration of short-term in vitro expanded ATCs from the same donor, might be a promising therapeutic option to improve the clinical outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tischer-Zimmermann, Salzer, Bitencourt, Frank, Hoffmann-Freimüller, Stemberger, Maecker-Kolhoff, Blasczyk, Witt, Fritsch, Paster, Lion, Eiz-Vesper and Geyeregger.)- Published
- 2023
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229. Reinforcement of cell-mediated immunity driven by tumor-associated Epstein-Barr virus (EBV)-specific T cells during targeted B-cell therapy with rituximab.
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Tischer-Zimmermann S, Bonifacius A, Santamorena MM, Mausberg P, Stoll S, Döring M, Kalinke U, Blasczyk R, Maecker-Kolhoff B, and Eiz-Vesper B
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- Humans, Herpesvirus 4, Human, Rituximab pharmacology, Rituximab therapeutic use, Immunity, Cellular, Antigens, Cell- and Tissue-Based Therapy, Epstein-Barr Virus Infections, Neoplasms
- Abstract
Introduction: In immunocompromised patients, Epstein-Barr virus (EBV) infection or reactivation is associated with increased morbidity and mortality, including the development of B-cell lymphomas. The first-line treatment consists of reduction of immunosuppression and administration of rituximab (anti-CD20 antibody). Furthermore, the presence of EBV-specific T cells against latent EBV proteins is crucial for the control of EBV-associated diseases. Therefore, in addition to effective treatment strategies, appropriate monitoring of T cells of high-risk patients is of great importance for improving clinical outcome. In this study, we hypothesized that rituximab-mediated lysis of malignant EBV-infected B cells leads to the release and presentation of EBV-associated antigens and results in an augmentation of EBV-specific effector memory T-cell responses., Methods: EBV-infected B lymphoblastoid cell lines (B-LCLs) were used as a model for EBV-associated lymphomas, which are capable of expressing latency stage II and III EBV proteins present in all known EBV-positive malignant cells. Rituximab was administered to obtain cell lysates containing EBV antigens (AC
EBV ). Efficiency of cross-presentation of EBV-antigen by B-LCLs compared to cross-presentation by professional antigen presenting cells (APCs) such as dendritic cells (DCs) and B cells was investigated by in vitro T-cell immunoassays. Deep T-cell profiling of the tumor-reactive EBV-specific T cells in terms of activation, exhaustion, target cell killing, and cytokine profile was performed, assessing the expression of T-cell differentiation and activation markers as well as regulatory and cytotoxic molecules by interferon-γ (IFN-γ) EliSpot assay, multicolor flow cytometry, and multiplex analyses., Results: By inhibiting parts of the cross-presentation pathway, B-LCLs were shown to cross-present obtained exogenous ACEBV -derived antigens mainly through major histocompatibility complex (MHC) class I molecules. This mechanism is comparable to that for DCs and B cells and resulted in a strong EBV-specific CD8+ cytotoxic T-cell response. Stimulation with ACEBV -loaded APCs also led to the activation of CD4+ T helper cells, suggesting that longer peptide fragments are processed via the classical MHC class II pathway. In addition, B-LCLs were also found to be able to take up exogenous antigens from surrounding cells by endocytosis leading to induction of EBV-specific T-cell responses although to a much lesser extent than cross-presentation of ACEBV -derived antigens. Increased expression of activation markers CD25, CD71 and CD137 were detected on EBV-specific T cells stimulated with ACEBV -loaded APCs, which showed high proliferative and cytotoxic capacity as indicated by enhanced EBV-specific frequencies and increased secretion levels of cytotoxic effector molecules (e.g. IFN-γ, granzyme B, perforin, and granulysin). Expression of the regulatory proteins PD-1 and Tim-3 was induced but had no negative impact on effector T-cell functions., Conclusion: In this study, we showed for the first time that rituximab-mediated lysis of EBV-infected tumor cells can efficiently boost EBV-specific endogenous effector memory T-cell responses through cross-presentation of EBV-derived antigens. This promotes the restoration of antiviral cellular immunity and presents an efficient mechanism to improve the treatment of CD20+ EBV-associated malignancies. This effect is also conceivable for other therapeutic antibodies or even for therapeutically applied unmodified or genetically modified T cells, which lead to the release of tumor antigens after specific cell lysis., Competing Interests: Author MD was employed and UK is employed by the Twincore Center for Experimental and Clinical Infection Research GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tischer-Zimmermann, Bonifacius, Santamorena, Mausberg, Stoll, Döring, Kalinke, Blasczyk, Maecker-Kolhoff and Eiz-Vesper.)- Published
- 2023
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230. [Thoracic medicine update].
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Zimmermann SC and Behr J
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- Humans, Pulmonary Disease, Chronic Obstructive, Asthma, Medicine
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- 2023
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231. Editorial: Beneficial microbes and the interconnection between crop mineral nutrition and induced systemic resistance, volume II.
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Lucena C, Aroca R, Wang J, and Zimmermann SD
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2023
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232. Editorial: Insights in plant symbiotic interactions: 2021.
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Genre A, Pawlowski K, Zimmermann SD, and Saia S
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Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2023
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233. Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy.
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Bonifacius A, Tischer-Zimmermann S, Santamorena MM, Mausberg P, Schenk J, Koch S, Barnstorf-Brandes J, Gödecke N, Martens J, Goudeva L, Verboom M, Wittig J, Maecker-Kolhoff B, Baurmann H, Clark C, Brauns O, Simon M, Lang P, Cornely OA, Hallek M, Blasczyk R, Seiferling D, Köhler P, and Eiz-Vesper B
- Abstract
Objectives: Evaluation of the feasibility of SARS-CoV-2-specific T cell manufacturing for adoptive T cell transfer in COVID-19 patients at risk to develop severe disease. Methods: Antiviral SARS-CoV-2-specific T cells were detected in blood of convalescent COVID-19 patients following stimulation with PepTivator SARS-CoV-2 Select using Interferon-gamma Enzyme-Linked Immunospot (IFN-γ ELISpot), SARS-CoV-2 T Cell Analysis Kit (Whole Blood) and Cytokine Secretion Assay (CSA) and were characterized with respect to memory phenotype, activation state and cytotoxic potential by multicolor flow cytometry, quantitative real-time PCR and multiplex analyses. Clinical-grade SARS-CoV-2-specific T cell products were generated by stimulation with MACS GMP PepTivator SARS-CoV-2 Select using CliniMACS Prodigy and CliniMACS Cytokine Capture System (IFN-gamma) (CCS). Functionality of enriched T cells was investigated in cytotoxicity assays and by multiplex analysis of secreted cytotoxic molecules upon target recognition. Results: Donor screening via IFN-γ ELISpot allows for pre-selection of potential donors for generation of SARS-CoV-2-specific T cells. Antiviral T cells reactive against PepTivator SARS-CoV-2 Select could be magnetically enriched from peripheral blood of convalescent COVID-19 patients by small-scale CSA resembling the clinical-grade CCS manufacturing process and showed an activated and cytotoxic T cell phenotype. Four clinical-grade SARS-CoV-2-specific T cell products were successfully generated with sufficient cell numbers and purities comparable to those observed in donor pretesting via CSA. The T cells in the generated products were shown to be capable to replicate, specifically recognize and kill target cells in vitro and secrete cytotoxic molecules upon target recognition. Cell viability, total CD3
+ cell number, proliferative capacity and cytotoxic potential remained stable throughout storage of up to 72 h after end of leukapheresis. Conclusion: Clinical-grade SARS-CoV-2-specific T cells are functional, have proliferative capacity and target-specific cytotoxic potential. Their function and phenotype remain stable for several days after enrichment. The adoptive transfer of partially matched, viable human SARS-CoV-2-specific T lymphocytes collected from convalescent individuals may provide the opportunity to support the immune system of COVID-19 patients at risk for severe disease., Competing Interests: OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; Consulting fees from Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Pfizer; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Jannsen, MedPace, Paratek, PSI, Shionogi; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, and Wiley. PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, medupdate GmbH, MedMedia, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC and University Hospital and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office; Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. Authors HB, CC, OB, and MS are employed by the company Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany. Author DS is employed by the company Miltenyi Biomedicine GmbH, Bergisch Gladbach, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bonifacius, Tischer-Zimmermann, Santamorena, Mausberg, Schenk, Koch, Barnstorf-Brandes, Gödecke, Martens, Goudeva, Verboom, Wittig, Maecker-Kolhoff, Baurmann, Clark, Brauns, Simon, Lang, Cornely, Hallek, Blasczyk, Seiferling, Köhler and Eiz-Vesper.)- Published
- 2022
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234. Antiviral T-Cell Frequencies in a Healthy Population: Reference Values for Evaluating Antiviral Immune Cell Profiles in Immunocompromised Patients.
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Schulze Lammers FC, Bonifacius A, Tischer-Zimmermann S, Goudeva L, Martens J, Lepenies B, von Karpowitz M, Einecke G, Beutel G, Skripuletz T, Blasczyk R, Beier R, Maecker-Kolhoff B, and Eiz-Vesper B
- Subjects
- Antiviral Agents, Herpesvirus 4, Human, Humans, Immunocompromised Host, Reference Values, T-Lymphocytes, Epstein-Barr Virus Infections, Hematopoietic Stem Cell Transplantation, Virus Diseases diagnosis
- Abstract
Viral infections and reactivations are major causes of morbidity and mortality after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) as well as in patients with immunodeficiencies. Latent herpesviruses (e.g., cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6), lytic viruses (e.g., adenovirus), and polyomaviruses (e.g., BK virus, JC virus) can cause severe complications. Antiviral drugs form the mainstay of treatment for viral infections and reactivations after transplantation, but they have side effects and cannot achieve complete viral clearance without prior reconstitution of functional antiviral T-cell immunity. The aim of this study was to establish normal ranges for virus-specific T-cell (VST) frequencies in healthy donors. Such data are needed for better interpretation of VST frequencies observed in immunocompromised patients. Therefore, we measured the frequencies of VSTs against 23 viral protein-derived peptide pools from 11 clinically relevant human viruses in blood from healthy donors (n = 151). Specifically, we determined the VST frequencies by interferon-gamma enzyme-linked immunospot assay and classified their distribution according to age and gender to allow for a more specific evaluation and prediction of antiviral immune responses. The reference values established here provide an invaluable tool for immune response evaluation, intensity of therapeutic drugs and treatment decision-making in immunosuppressed patients. This data should make an important contribution to improving the assessment of immune responses in immunocompromised patients., (© 2022. The Author(s).)
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- 2022
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235. Corrigendum to: pH biosensing in the plant apoplast-a focus on root cell elongation.
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Moreau H, Zimmermann SD, Gaillard I, and Paris N
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- 2021
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236. Editorial: Beneficial Microbes and the Interconnection Between Crop Mineral Nutrition and Induced Systemic Resistance.
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Lucena C, Zimmermann SD, Wang J, and Aroca R
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2021
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237. Long-Lasting Immunity Against SARS-CoV-2: Dream or Reality?
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Gussarow D, Bonifacius A, Cossmann A, Stankov MV, Mausberg P, Tischer-Zimmermann S, Gödecke N, Kalinke U, Behrens GMN, Blasczyk R, and Eiz-Vesper B
- Abstract
Since its declaration as a pandemic in March 2020, SARS-CoV-2 has infected more than 217 million people worldwide and despite mild disease in the majority of the cases, more than 4.5 million cases of COVID-19-associated death have been reported as of September 2021. The question whether recovery from COVID-19 results in prevention of reinfection can be answered with a "no" since cases of reinfections have been reported. The more important question is whether during SARS-CoV-2 infection, a protective immunity is built and maintained afterwards in a way which protects from possibly severe courses of disease in case of a reinfection. A similar question arises with respect to vaccination: as of September 2021, globally, more than 5.2 billion doses of vaccines have been administered. Therefore, it is of utmost importance to study the cellular and humoral immunity toward SARS-CoV-2 in a longitudinal manner. In this study, reconvalescent COVID-19 patients have been followed up for more than 1 year after SARS-CoV-2 infection to characterize in detail the long-term humoral as well as cellular immunity. Both SARS-CoV-2-specific T cells and antibodies could be detected for a period of more than 1 year after infection, indicating that the immune protection established during initial infection is maintained and might possibly protect from severe disease in case of reinfection or infection with novel emerging variants. Moreover, these data demonstrate the opportunity for immunotherapy of hospitalized COVID-19 patients via adoptive transfer of functional antiviral T cells isolated from reconvalescent individuals., Competing Interests: UK is employed by the Helmholtz Centre for Infection Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gussarow, Bonifacius, Cossmann, Stankov, Mausberg, Tischer-Zimmermann, Gödecke, Kalinke, Behrens, Blasczyk and Eiz-Vesper.)
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- 2021
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238. pH biosensing in the plant apoplast-a focus on root cell elongation.
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Moreau H, Zimmermann SD, Gaillard I, and Paris N
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- Cell Enlargement, Hydrogen-Ion Concentration, Plant Roots cytology, Plant Roots genetics, Biosensing Techniques methods, Fluorescent Dyes, Luminescent Proteins genetics, Plant Roots growth & development
- Abstract
The pH parameter of soil plays a key role for plant nutrition as it is affecting the availability of minerals and consequently determines plant growth. Although the mechanisms by which root perceive the external pH is still unknown, the impact of external pH on tissue growth has been widely studied especially in hypocotyl and root. Thanks to technological development of cell imaging and fluorescent sensors, we can now monitor pH in real time with at subcellular definition. In this focus, fluorescent dye-based, as well as genetically-encoded pH indicators are discussed especially with respect to their ability to monitor acidic pH in the context of primary root. The notion of apoplastic subdomains is discussed and suggestions are made to develop fluorescent indicators for pH values below 5.0., (© American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2021
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239. Variances in Antiviral Memory T-Cell Repertoire of CD45RA- and CD62L-Depleted Lymphocyte Products Reflect the Need of Individual T-Cell Selection Strategies to Reduce the Risk of GvHD while Preserving Antiviral Immunity in Adoptive T-Cell Therapy.
- Author
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Mangare C, Tischer-Zimmermann S, Bonifacius A, Riese SB, Dragon AC, Blasczyk R, Maecker-Kolhoff B, and Eiz-Vesper B
- Abstract
Introduction: Viral infections and reactivations still remain a cause of morbidity and mortality after hematopoietic stem cell transplantation due to immunodeficiency and immunosuppression. Transfer of unmanipulated donor-derived lymphocytes (DLI) represents a promising strategy for improving cellular immunity but carries the risk of graft versus host disease (GvHD). Depleting alloreactive naïve T cells (T
N ) from DLIs was implemented to reduce the risk of GvHD induction while preserving antiviral memory T-cell activity. Here, we compared two TN depletion strategies via CD45RA and CD62L expression and investigated the presence of antiviral memory T cells against human adenovirus (AdV) and Epstein-Barr virus (EBV) in the depleted fractions in relation to their functional and immunophenotypic characteristics., Methods: T-cell responses against ppEBV_EBNA1, ppEBV_Consensus and ppAdV_Hexon within TN -depleted (CD45RA- /CD62L- ) and TN -enriched (CD45RA+ /CD62L+ ) fractions were quantified by interferon-gamma (IFN-γ) ELISpot assay after short- and long-term in vitro stimulation. T-cell frequencies and immunophenotypic composition were assessed in all fractions by flow cytometry. Moreover, alloimmune T-cell responses were evaluated by mixed lymphocyte reaction., Results: According to differences in the phenotype composition, antigen-specific T-cell responses in CD45RA- fraction were up to 2 times higher than those in the CD62L- fraction, with the highest increase (up to 4-fold) observed after 7 days for ppEBV_EBNA1-specific T cells. The CD4+ effector memory T cells (TEM ) were mainly responsible for EBV_EBNA1- and AdV_Hexon-specific T-cell responses, whereas the main functionally active T cells against ppEBV_Consensus were CD8+ central memory T cells (TCM ) and TEM . Moreover, comparison of both depletion strategies indicated that alloreactivity in CD45RA- was lower than that in CD62L- fraction., Conclusion: Taken together, our results indicate that CD45RA depletion is a more suitable strategy for generating TN -depleted products consisting of memory T cells against ppEBV_EBNA1 and ppAdV_Hexon than CD62L in terms of depletion effectiveness, T-cell functionality and alloreactivity. To maximally exploit the beneficial effects mediated by antiviral memory T cells in TN -depleted products, depletion methods should be selected individually according to phenotype composition and CD4/CD8 antigen restriction. TN -depleted DLIs may improve the clinical outcome in terms of infections, GvHD, and disease relapse if selection of pathogen-specific donor T cells is not available., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by S. Karger AG, Basel.)- Published
- 2021
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240. COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses.
- Author
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Bonifacius A, Tischer-Zimmermann S, Dragon AC, Gussarow D, Vogel A, Krettek U, Gödecke N, Yilmaz M, Kraft ARM, Hoeper MM, Pink I, Schmidt JJ, Li Y, Welte T, Maecker-Kolhoff B, Martens J, Berger MM, Lobenwein C, Stankov MV, Cornberg M, David S, Behrens GMN, Witzke O, Blasczyk R, and Eiz-Vesper B
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Viral blood, Antibodies, Viral immunology, Female, Humans, Immunity, Humoral immunology, Male, Middle Aged, SARS-CoV-2 immunology, Young Adult, CD4-Positive T-Lymphocytes immunology, COVID-19 immunology, Immunity, Cellular immunology
- Abstract
Cellular and humoral immunity to SARS-CoV-2 is critical to control primary infection and correlates with severity of disease. The role of SARS-CoV-2-specific T cell immunity, its relationship to antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in 82 healthy donors (HDs), 204 recovered (RCs), and 92 active COVID-19 patients (ACs). ACs had high amounts of anti-SARS-CoV-2 nucleocapsid and spike IgG but lymphopenia and overall reduced antiviral T cell responses due to the inflammatory milieu, expression of inhibitory molecules (PD-1, Tim-3) as well as effector caspase-3, -7, and -8 activity in T cells. SARS-CoV-2-specific T cell immunity conferred by polyfunctional, mainly interferon-γ-secreting CD4
+ T cells remained stable throughout convalescence, whereas humoral responses declined. Immune responses toward huCoV in RCs with mild disease and strong cellular SARS-CoV-2 T cell reactivity imply a protective role of pre-existing immunity against huCoV., Competing Interests: Declaration of interests The authors declare that they have no competing interests. The funders played no role in designing the study, in collecting, analyzing, or interpreting the data, in writing the manuscript, or in the decision to publish the results., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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241. Higher body mass index is associated with increased lung stiffness and less airway obstruction in individuals with asthma and fixed airflow obstruction.
- Author
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Rutting S, Chapman DG, Badal T, Sanai F, Zimmermann SC, Thamrin C, King GG, and Tonga KO
- Abstract
Higher body mass index (BMI) is associated with less severe airway obstruction in older asthma patients with fixed airflow obstruction. This is potentially mediated through BMI-related mechanisms that increase lung stiffness ( i.e. reduce lung compliance). https://bit.ly/3jBwCNy., Competing Interests: Conflict of interest: S. Rutting has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: T. Badal has nothing to disclose. Conflict of interest: F. Sanai has nothing to disclose. Conflict of interest: S.C. Zimmermann reports nonfinancial support for travel and accommodation for educational respiratory symposia attendance from GlaxoSmithKline, Boehringer Ingelheim, Menarini, AstraZeneca and Novartis, outside the submitted work. Conflict of interest: C. Thamrin has nothing to disclose. Conflict of interest: G.G. King reports unrestricted research grants to support research projects, fees for consultancy services (which include lectures and advisory board services) and conference attendance support from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Menarini and MundiPharma, and research grants from the National Health & Medical Research Council, professional societies, The University of Sydney, and philanthropic individuals and societies, outside the submitted work. Conflict of interest: K.O. Tonga has nothing to disclose., (Copyright ©ERS 2021.)
- Published
- 2021
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242. Fungal Shaker-like channels beyond cellular K+ homeostasis: A role in ectomycorrhizal symbiosis between Hebeloma cylindrosporum and Pinus pinaster.
- Author
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Garcia K, Guerrero-Galán C, Frank HER, Haider MZ, Delteil A, Conéjéro G, Lambilliotte R, Fizames C, Sentenac H, and Zimmermann SD
- Subjects
- Potassium metabolism, Fungal Proteins biosynthesis, Gene Expression Regulation, Fungal physiology, Hebeloma physiology, Mycorrhizae physiology, Pinus microbiology, Pinus physiology, Shaker Superfamily of Potassium Channels biosynthesis, Symbiosis physiology
- Abstract
Potassium (K+) acquisition, translocation and cellular homeostasis are mediated by various membrane transport systems in all organisms. We identified and described an ion channel in the ectomycorrhizal fungus Hebeloma cylindrosporum (HcSKC) that harbors features of animal voltage-dependent Shaker-like K+ channels, and investigated its role in both free-living hyphae and symbiotic conditions. RNAi lines affected in the expression of HcSKC were produced and used for in vitro mycorrhizal assays with the maritime pine as host plant, under standard or low K+ conditions. The adaptation of H. cylindrosporum to the downregulation of HcSKC was analyzed by qRT-PCR analyses for other K+-related transport proteins: the transporters HcTrk1, HcTrk2, and HcHAK, and the ion channels HcTOK1, HcTOK2.1, and HcTOK2.2. Downregulated HcSKC transformants displayed greater K+ contents at standard K+ only. In such conditions, plants inoculated with these transgenic lines were impaired in K+ nutrition. Taken together, these results support the hypothesis that the reduced expression of HcSKC modifies the pool of fungal K+ available for the plant and/or affects its symbiotic transfer to the roots. Our study reveals that the maintenance of K+ transport in H. cylindrosporum, through the regulation of HcSKC expression, is required for the K+ nutrition of the host plant., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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243. New insights into HcPTR2A and HcPTR2B, two high-affinity peptide transporters from the ectomycorrhizal model fungus Hebeloma cylindrosporum.
- Author
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Müller T, Neuhäuser B, Ludewig U, Houdinet G, Zimmermann SD, Courty PE, and Wipf D
- Subjects
- Gene Expression Regulation, Fungal, Hebeloma genetics, Membrane Transport Proteins genetics, Mycorrhizae
- Abstract
While plants mainly rely on the use of inorganic nitrogen sources like ammonium and nitrate, soil-borne microorganisms like the ectomycorrhizal fungus Hebeloma cylindrosporum can also take up soil organic N in the form of amino acids and peptides that they use as nitrogen and carbon sources. Following the previous identification and functional expression in yeast of two PTR-like peptide transporters, the present study details the functions and substrates of HcPTR2A and HcPTR2B by analysing their transport kinetics in Xenopus laevis oocytes. While both transporters mediated high-affinity di- and tripeptide transport, HcPTR2A also showed low-affinity transport of several amino acids-mostly hydrophobic ones with large side chains.
- Published
- 2020
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244. CAR-T cells and TRUCKs that recognize an EBNA-3C-derived epitope presented on HLA-B*35 control Epstein-Barr virus-associated lymphoproliferation.
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Dragon AC, Zimmermann K, Nerreter T, Sandfort D, Lahrberg J, Klöß S, Kloth C, Mangare C, Bonifacius A, Tischer-Zimmermann S, Blasczyk R, Maecker-Kolhoff B, Uchanska-Ziegler B, Abken H, Schambach A, Hudecek M, and Eiz-Vesper B
- Subjects
- Female, Humans, Male, Epitopes metabolism, Epstein-Barr Virus Nuclear Antigens metabolism, HLA-B Antigens metabolism, Immunotherapy, Adoptive methods
- Abstract
Background: Immunosuppressive therapy or T-cell depletion in transplant patients can cause uncontrolled growth of Epstein-Barr virus (EBV)-infected B cells resulting in post-transplant lymphoproliferative disease (PTLD). Current treatment options do not distinguish between healthy and malignant B cells and are thereby often limited by severe side effects in the already immunocompromised patients. To specifically target EBV-infected B cells, we developed a novel peptide-selective chimeric antigen receptor (CAR) based on the monoclonal antibody TÜ165 which recognizes an Epstein-Barr nuclear antigen (EBNA)-3C-derived peptide in HLA-B*35 context in a T-cell receptor (TCR)-like manner. In order to attract additional immune cells to proximity of PTLD cells, based on the TÜ165 CAR, we moreover generated T cells redirected for universal cytokine-mediated killing (TRUCKs), which induce interleukin (IL)-12 release on target contact., Methods: TÜ165-based CAR-T cells (CAR-Ts) and TRUCKs with inducible IL-12 expression in an all-in-one construct were generated. Functionality of the engineered cells was assessed in co-cultures with EBNA-3C-peptide-loaded, HLA-B*35-expressing K562 cells and EBV-infected B cells as PTLD model. IL-12, secreted by TRUCKs on target contact, was further tested for its chemoattractive and activating potential towards monocytes and natural killer (NK) cells., Results: After co-cultivation with EBV target cells, TÜ165 CAR-Ts and TRUCKs showed an increased activation marker expression (CD137, CD25) and release of proinflammatory cytokines (interferon-γ and tumor necrosis factor-α). Moreover, TÜ165 CAR-Ts and TRUCKs released apoptosis-inducing mediators (granzyme B and perforin) and were capable to specifically lyse EBV-positive target cells. Live cell imaging revealed a specific attraction of TÜ165 CAR-Ts around EBNA-3C-peptide-loaded target cells. Of note, TÜ165 TRUCKs with inducible IL-12 showed highly improved effector functions and additionally led to recruitment of monocyte and NK cell lines., Conclusions: Our results demonstrate that TÜ165 CAR-Ts recognize EBV peptide/HLA complexes in a TCR-like manner and thereby allow for recognizing an intracellular EBV target. TÜ165 TRUCKs equipped with inducible IL-12 expression responded even more effectively and released IL-12 recruited additional immune cells which are generally missing in proximity of lymphoproliferation in immunocompromised PTLD patients. This suggests a new and promising strategy to specifically target EBV-infected cells while sparing and mobilizing healthy immune cells and thereby enable control of EBV-associated lymphoproliferation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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245. High-intensity interval training in allogeneic adoptive T-cell immunotherapy - a big HIT?
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Heinemann NC, Tischer-Zimmermann S, Wittke TC, Eigendorf J, Kerling A, Framke T, Melk A, Heuft HG, Blasczyk R, Maecker-Kolhoff B, and Eiz-Vesper B
- Subjects
- Immunotherapy, Adoptive, Pilot Projects, T-Lymphocytes, Hematopoietic Stem Cell Transplantation, High-Intensity Interval Training
- Abstract
Background: Adoptive transfer of virus-specific T cells (VSTs) represents a prophylactic and curative approach for opportunistic viral infections and reactivations after transplantation. However, inadequate frequencies of circulating memory VSTs in the T-cell donor's peripheral blood often result in insufficient enrichment efficiency and purity of the final T-cell product, limiting the effectiveness of this approach., Methods: This pilot study was designed as a cross-over trial and compared the effect of a single bout (30 min) of high-intensity interval training (HIT) with that of 30 min of continuous exercise (CONT) on the frequency and function of circulating donor VSTs. To this end, we used established immunoassays to examine the donors' cellular immune status, in particular, with respect to the frequency and specific characteristics of VSTs restricted against Cytomegalovirus (CMV)-, Epstein-Barr-Virus (EBV)- and Adenovirus (AdV)-derived antigens. T-cell function, phenotype, activation and proliferation were examined at different time points before and after exercise to identify the most suitable time for T-cell donation. The clinical applicability was determined by small-scale T-cell enrichment using interferon- (IFN-) γ cytokine secretion assay and virus-derived overlapping peptide pools., Results: HIT proved to be the most effective exercise program with up to fivefold higher VST response. In general, donors with a moderate fitness level had higher starting and post-exercise frequencies of VSTs than highly fit donors, who showed significantly lower post-exercise increases in VST frequencies. Both exercise programs boosted the number of VSTs against less immunodominant antigens, specifically CMV (IE-1), EBV (EBNA-1) and AdV (Hexon, Penton), compared to VSTs against immunodominant antigens with higher memory T-cell frequencies., Conclusion: This study demonstrates that exercise before T-cell donation has a beneficial effect on the donor's cellular immunity with respect to the proportion of circulating functionally active VSTs. We conclude that a single bout of HIT exercise 24 h before T-cell donation can significantly improve manufacturing of clinically applicable VSTs. This simple and economical adjuvant treatment proved to be especially efficient in enhancing virus-specific memory T cells with low precursor frequencies.
- Published
- 2020
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246. Refractory Epstein-Barr Virus (EBV)-Related Post-transplant Lymphoproliferative Disease: Cure by Combined Brentuximab Vedotin and Allogeneic EBV-Specific T-Lymphocytes.
- Author
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Mika T, Strate K, Ladigan S, Aigner C, Schlegel U, Tischoff I, Tischer-Zimmermann S, Eiz-Vesper B, Maecker-Kolhoff B, and Schroers R
- Abstract
Post-transplant lymphoproliferative disease (PTLD) represents a serious complication following allogeneic hematopoietic stem cell transplantation (alloHSCT). Previously, survival rates of PTLD have improved due to the introduction of rituximab. However, reports on curative management of refractory PTLD are scarce. Today, there is no consensus how to treat rituximab-refractory PTLD, especially in highly aggressive disease. Here, we describe successful management of refractory EBV-associated PTLD, specifically DLBCL, with combined brentuximab vedotin and third-party EBV-specific T-cells in a multidisciplinary treatment approach., (Copyright © 2019 Mika, Strate, Ladigan, Aigner, Schlegel, Tischoff, Tischer-Zimmermann, Eiz-Vesper, Maecker-Kolhoff and Schroers.)
- Published
- 2019
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247. Ectomycorrhizal symbiosis helps plants to challenge salt stress conditions.
- Author
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Guerrero-Galán C, Calvo-Polanco M, and Zimmermann SD
- Subjects
- Plant Roots growth & development, Sodium metabolism, Water metabolism, Fungi physiology, Mycorrhizae physiology, Plant Roots microbiology, Plant Roots physiology, Salt Stress, Symbiosis
- Abstract
Soil salinity is an environmental condition that is currently increasing worldwide. Plant growth under salinity induces osmotic stress and ion toxicity impairing root water and nutrient absorption, but the association with beneficial soil microorganisms has been linked to an improved adaptation to this constraint. The ectomycorrhizal (ECM) symbiosis has been proposed as a key factor for a better tolerance of woody species to salt stress, thanks to the reduction of sodium (Na
+ ) uptake towards photosynthetic organs. Although no precise mechanisms for this enhanced plant salt tolerance have been described yet, in this review, we summarize the knowledge accumulated so far on the role of ECM symbiosis. Moreover, we propose several strategies by which ECM fungi might help plants, including restriction of Na+ entrance into plant tissues and improvement of mineral nutrition and water balances. This positive effect of ECM fungi has been proven in field assays and the results obtained point to a promising application in forestry cultures and reforestation.- Published
- 2019
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248. Discrepancy between in vivo and in vitro comparisons of forced oscillation devices.
- Author
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Zimmermann SC, Watts JC, Bertolin A, Jetmalani K, King GG, and Thamrin C
- Subjects
- Adult, Female, Healthy Volunteers, Humans, In Vitro Techniques, Male, Monitoring, Physiologic, Reproducibility of Results, Respiration, Signal Processing, Computer-Assisted, Software, Young Adult, Equipment Design, Oscillometry methods, Respiratory Function Tests instrumentation, Respiratory Function Tests methods
- Abstract
The forced oscillation technique (FOT) is an emerging clinical lung function test, with commercial devices becoming increasingly available. However comparability across existing devices has not been established. We evaluated in vivo and in vitro measurements made using three commercial devices against a custom-built device (WIMR): Resmon Pro Diary (Restech srl, Italy), tremoFlo C-100 (Thorasys Medical Systems, Canada), Jaeger Masterscope CT IOS (CareFusion, Hoechberg, Germany). Respiratory system resistance Rrs and reactance Xrs at 5 Hz were examined in twelve healthy subjects (mean age 33 ± 11 years, 7 males), and in two test standards of known resistance and reactance. Subjects performed three measurements during tidal breathing on the four devices in random order. Total, inspiratory and expiratory Rrs and Xrs were calculated and compared using one-way repeated measures ANOVA and Bonferroni post-hoc tests. Rrs did not differ between devices, with <10% deviation from predicted, except for the IOS device. With Xrs, similar values were seen between the WIMR and Resmon devices and between the tremoFlo and IOS devices. No differences were observed using test standards; deviation from theoretical value was <2% for resistance and <5% for reactance. The WIMR, tremoFlo and Resmon Pro but not IOS devices measure similar Rrs, whereas there was more disparity across devices in the estimation of Xrs parameters. The discrepancy between in vivo and in vitro measurements suggest that FOT validation procedures need to take into account the breathing pattern, either using biological controls or a breathing model.
- Published
- 2018
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249. Distinct amino acids in the C-linker domain of the Arabidopsis K+ channel KAT2 determine its subcellular localization and activity at the plasma membrane.
- Author
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Nieves-Cordones M, Chavanieu A, Jeanguenin L, Alcon C, Szponarski W, Estaran S, Chérel I, Zimmermann S, Sentenac H, and Gaillard I
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Amino Acid Substitution, Ion Channel Gating, Models, Molecular, Molecular Sequence Data, Point Mutation genetics, Protein Structure, Tertiary, Protein Transport, Sequence Deletion genetics, Structural Homology, Protein, Structure-Activity Relationship, Subcellular Fractions metabolism, Amino Acids metabolism, Arabidopsis metabolism, Arabidopsis Proteins chemistry, Arabidopsis Proteins metabolism, Cell Membrane metabolism, Potassium Channels, Voltage-Gated chemistry, Potassium Channels, Voltage-Gated metabolism
- Abstract
Shaker K(+) channels form the major K(+) conductance of the plasma membrane in plants. They are composed of four subunits arranged around a central ion-conducting pore. The intracellular carboxy-terminal region of each subunit contains several regulatory elements, including a C-linker region and a cyclic nucleotide-binding domain (CNBD). The C-linker is the first domain present downstream of the sixth transmembrane segment and connects the CNBD to the transmembrane core. With the aim of identifying the role of the C-linker in the Shaker channel properties, we performed subdomain swapping between the C-linker of two Arabidopsis (Arabidopsis thaliana) Shaker subunits, K(+) channel in Arabidopsis thaliana2 (KAT2) and Arabidopsis thaliana K(+) rectifying channel1 (AtKC1). These two subunits contribute to K(+) transport in planta by forming heteromeric channels with other Shaker subunits. However, they display contrasting behavior when expressed in tobacco mesophyll protoplasts: KAT2 forms homotetrameric channels active at the plasma membrane, whereas AtKC1 is retained in the endoplasmic reticulum when expressed alone. The resulting chimeric/mutated constructs were analyzed for subcellular localization and functionally characterized. We identified two contiguous amino acids, valine-381 and serine-382, located in the C-linker carboxy-terminal end, which prevent KAT2 surface expression when mutated into the equivalent residues from AtKC1. Moreover, we demonstrated that the nine-amino acid stretch 312TVRAASEFA320 that composes the first C-linker α-helix located just below the pore is a crucial determinant of KAT2 channel activity. A KAT2 C-linker/CNBD three-dimensional model, based on animal HCN (for Hyperpolarization-activated, cyclic nucleotide-gated K(+)) channels as structure templates, has been built and used to discuss the role of the C-linker in plant Shaker inward channel structure and function.
- Published
- 2014
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250. Potassium nutrition of ectomycorrhizal Pinus pinaster: overexpression of the Hebeloma cylindrosporum HcTrk1 transporter affects the translocation of both K(+) and phosphorus in the host plant.
- Author
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Garcia K, Delteil A, Conéjéro G, Becquer A, Plassard C, Sentenac H, and Zimmermann S
- Subjects
- Biological Transport drug effects, DNA, Bacterial genetics, Gene Expression Regulation, Fungal drug effects, Hebeloma drug effects, Hebeloma genetics, Hyphae drug effects, Hyphae metabolism, Mycorrhizae drug effects, Mycorrhizae genetics, Phenotype, Phosphorus pharmacology, Pinus drug effects, Pinus microbiology, Potassium pharmacology, RNA, Messenger genetics, RNA, Messenger metabolism, Seedlings drug effects, Seedlings metabolism, Seedlings microbiology, Sodium metabolism, Fungal Proteins metabolism, Hebeloma metabolism, Host-Pathogen Interactions drug effects, Mycorrhizae metabolism, Phosphorus metabolism, Pinus metabolism, Potassium metabolism
- Abstract
Mycorrhizal associations are known to improve the hydro-mineral nutrition of their host plants. However, the importance of mycorrhizal symbiosis for plant potassium nutrition has so far been poorly studied. We therefore investigated the impact of the ectomycorrhizal fungus Hebeloma cylindrosporum on the potassium nutrition of Pinus pinaster and examined the involvement of the fungal potassium transporter HcTrk1. HcTrk1 transcripts and proteins were localized in ectomycorrhizas using in situ hybridization and EGFP translational fusion constructs. Importantly, an overexpression strategy was performed on a H. cylindrosporum endogenous gene in order to dissect the role of this transporter. The potassium nutrition of mycorrhizal pine plants was significantly improved under potassium-limiting conditions. Fungal strains overexpressing HcTrk1 reduced the translocation of potassium and phosphorus from the roots to the shoots of inoculated plants in mycorrhizal experiments. Furthermore, expression of HcTrk1 and the phosphate transporter HcPT1.1 were reciprocally linked to the external inorganic phosphate and potassium availability. The development of these approaches provides a deeper insight into the role of ectomycorrhizal symbiosis on host plant K(+) nutrition and in particular, the K(+) transporter HcTrk1. The work augments our knowledge of the link between potassium and phosphorus nutrition via the mycorrhizal pathway., (© 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.)
- Published
- 2014
- Full Text
- View/download PDF
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