TY - JOUR A1 - Vellmer, Tim A1 - Hartleb, Laura A1 - Fradera Sola, Albert A1 - Kramer, Susanne A1 - Meyer-Natus, Elisabeth A1 - Butter, Falk A1 - Janzen, Christian J. T1 - A novel SNF2 ATPase complex in Trypanosoma brucei with a role in H2A.Z-mediated chromatin remodelling JF - PLoS Pathogens N2 - A cascade of histone acetylation events with subsequent incorporation of a histone H2A variant plays an essential part in transcription regulation in various model organisms. A key player in this cascade is the chromatin remodelling complex SWR1, which replaces the canonical histone H2A with its variant H2A.Z. Transcriptional regulation of polycistronic transcription units in the unicellular parasite Trypanosoma brucei has been shown to be highly dependent on acetylation of H2A.Z, which is mediated by the histone-acetyltransferase HAT2. The chromatin remodelling complex which mediates H2A.Z incorporation is not known and an SWR1 orthologue in trypanosomes has not yet been reported. In this study, we identified and characterised an SWR1-like remodeller complex in T. brucei that is responsible for Pol II-dependent transcriptional regulation. Bioinformatic analysis of potential SNF2 DEAD/Box helicases, the key component of SWR1 complexes, identified a 1211 amino acids-long protein that exhibits key structural characteristics of the SWR1 subfamily. Systematic protein-protein interaction analysis revealed the existence of a novel complex exhibiting key features of an SWR1-like chromatin remodeller. RNAi-mediated depletion of the ATPase subunit of this complex resulted in a significant reduction of H2A.Z incorporation at transcription start sites and a subsequent decrease of steady-state mRNA levels. Furthermore, depletion of SWR1 and RNA-polymerase II (Pol II) caused massive chromatin condensation. The potential function of several proteins associated with the SWR1-like complex and with HAT2, the key factor of H2A.Z incorporation, is discussed. KW - Trypanosoma KW - chromatin KW - histones KW - RNA interference KW - Trypanosoma brucei gambiense KW - luciferase KW - transcriptional control KW - nucleosomes Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301372 VL - 18 IS - 6 ER - TY - JOUR A1 - Sathyanarayana, Vijaya A1 - Lee, Beth A1 - Wright, Neville B. A1 - Santos, Rui A1 - Bonney, Denise A1 - Wynn, Robert A1 - Patel, Leena A1 - Chandler, Kate A1 - Cheesman, Ed A1 - Schindler, Detlev A1 - Webb, Nicholas J. A. A1 - Meyer, Stefan T1 - Patterns and frequency of renal abnormalities in Fanconi anaemia: implications for long-term management JF - Pediatric Nephrology N2 - Fanconi anaemia (FA) is an inherited disease with bone marrow failure, variable congenital and developmental abnormalities, and cancer predisposition. With improved survival, non-haematological manifestations of FA become increasingly important for long-term management. While renal abnormalities are recognized, detailed data on patterns and frequency and implications for long-term management are sparse. We reviewed clinical course and imaging findings of FA patients with respect to renal complications in our centre over a 25-year period to formulate some practical suggestions for guidelines for management of renal problems associated with FA. Thirty patients including four sibling sets were reviewed. On imaging, 14 had evidence of anatomical abnormalities of the kidneys. Two cases with severe phenotype, including renal abnormalities, had chronic kidney disease (CKD) at diagnosis. Haematopoietic stem cell transplantation was complicated by significant acute kidney injury (AKI) in three cases. In three patients, there was CKD at long-term follow-up. All patients had normal blood pressure. Evaluation of renal anatomy with ultrasound imaging is important at diagnostic workup of FA. While CKD is uncommon at diagnosis, our data suggests that the incidence of CKD increases with age, in particular after haematopoietic stem cell transplantation. Monitoring of renal function is essential for management of FA. Based on these long-term clinical observations, we formulate some practical guidelines for assessment and management of renal abnormalities in FA. KW - Fanconi anaemia KW - Renal abnormalities KW - Long-term follow-up Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227400 VL - 33 IS - 9 ER - TY - JOUR A1 - Dindas, Julian A1 - Scherzer, Sönke A1 - Roelfsema, M. Rob G. A1 - Meyer, Katharina von A1 - Müller, Heike M. A1 - Al-Rasheid, K. A. S. A1 - Palme, Klaus A1 - Dietrich, Petra A1 - Becker, Dirk A1 - Bennett, Malcolm J. A1 - Hedrich, Rainer T1 - AUX1-mediated root hair auxin influx governs SCFTIR1/AFB-type Ca2+ signaling JF - Nature Communications N2 - Auxin is a key regulator of plant growth and development, but the causal relationship between hormone transport and root responses remains unresolved. Here we describe auxin uptake, together with early steps in signaling, in Arabidopsis root hairs. Using intracellular microelectrodes we show membrane depolarization, in response to IAA in a concentration- and pH-dependent manner. This depolarization is strongly impaired in aux1 mutants, indicating that AUX1 is the major transporter for auxin uptake in root hairs. Local intracellular auxin application triggers Ca2+ signals that propagate as long-distance waves between root cells and modulate their auxin responses. AUX1-mediated IAA transport, as well as IAA- triggered calcium signals, are blocked by treatment with the SCFTIR1/AFB - inhibitor auxinole. Further, they are strongly reduced in the tir1afb2afb3 and the cngc14 mutant. Our study reveals that the AUX1 transporter, the SCFTIR1/AFB receptor and the CNGC14 Ca2+ channel, mediate fast auxin signaling in roots. KW - auxin KW - permeation and transport Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225368 VL - 9 ER - TY - JOUR A1 - Leopold, Karolina A1 - Bauer, Michael A1 - Bechdolf, Andreas A1 - Correll, Christoph U. A1 - Holtmann, Martin A1 - Juckel, Georg A1 - Lambert, Martin A1 - Meyer, Thomas D. A1 - Pfeiffer, Steffi A1 - Kittel‐Schneider, Sarah A1 - Reif, Andreas A1 - Stamm, Thomas J. A1 - Rottmann‐Wolf, Maren A1 - Mathiebe, Josephine A1 - Kellmann, Eva L. A1 - Ritter, Philipp A1 - Krüger‐Özgürdal, Seza A1 - Karow, Anne A1 - Sondergeld, Lene‐Marie A1 - Roessner, Veit A1 - Sauer, Cathrin A1 - Pfennig, Andrea T1 - Efficacy of cognitive‐behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study JF - Bipolar Disorders N2 - Objective Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at‐risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive‐behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms. Method In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15‐30 years were randomized to 14 weeks of at‐risk for BD‐specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14 weeks. At‐risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75% of the targeted sample. Results Of 128 screened participants, 75 were randomized to group CBT (n = 38, completers = 65.8%) vs unstructured group meetings (n = 37, completers = 78.4%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P < .001) and during 6 months (P < .001) in both groups, without significant between‐group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop‐outs. Conclusions Results suggest that young patients at‐risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification. KW - at‐risk KW - bipolar disorder KW - CBT KW - early intervention KW - group treatment KW - prodromal KW - serious mental illness KW - subthreshold bipolar Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215469 VL - 22 IS - 5 SP - 517 EP - 529 ER - TY - JOUR A1 - Doppler, Christopher E. J. A1 - Meyer, Linda A1 - Dovern, Anna A1 - Stühmer-Beckh, Jaro A1 - Weiss, Peter H. A1 - Fink, Gereon R. T1 - Differential impact of social and monetary reward on procedural learning and consolidation in aging and its structural correlates JF - Frontiers in Aging Neuroscience N2 - In young (n = 36, mean +/- SD: 24.8 +/- 4.5 years) and older (n = 34, mean +/- SD: 65.1 +/- 6.5 years) healthy participants, we employed a modified version of the Serial Reaction Time task to measure procedural learning (PL) and consolidation while providing monetary and social reward. Using voxel-based morphometry (VBM), we additionally determined the structural correlates of reward-related motor performance (RMP) and PL. Monetary reward had a beneficial effect on PL in the older subjects only. In contrast, social reward significantly enhanced PL in the older and consolidation in the young participants. VBM analyses revealed that motor performance related to monetary reward was associated with larger grey matter volume (GMV) of the left striatum in the young, and motor performance related to social reward with larger GMV of the medial orbitofrontal cortex in the older group. The differential effects of social reward in young (improved consolidation) and both social and monetary rewards in older (enhanced PL) healthy subjects point to the potential of rewards for interventions targeting aging-associated motor decline or stroke-induced motor deficits. KW - serial reaction time task KW - procedural learning KW - reinforcement learning KW - voxel-based morphometry KW - motor aging Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222394 VL - 11 ER -