@article{StotzMuellerZoelleretal.2013, author = {Stotz, Henrik U. and Mueller, Stefan and Zoeller, Maria and Mueller, Martin J. and Berger, Susanne}, title = {TGA transcription factors and jasmonate-independent COI1 signalling regulate specific plant responses to reactive oxylipins}, series = {Journal of Experimental Botany}, volume = {64}, journal = {Journal of Experimental Botany}, number = {4}, doi = {10.1093/jxb/ers389}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132318}, pages = {963-975}, year = {2013}, abstract = {Jasmonates and phytoprostanes are oxylipins that regulate stress responses and diverse physiological and developmental processes. 12-Oxo-phytodienoic acid (OPDA) and phytoprostanes are structurally related electrophilic cyclopentenones, which activate similar gene expression profiles that are for the most part different from the action of the cyclopentanone jasmonic acid (JA) and its biologically active amino acid conjugates. Whereas JA-isoleucine signals through binding to COI1, the bZIP transcription factors TGA2, TGA5, and TGA6 are involved in regulation of gene expression in response to phytoprostanes. Here root growth inhibition and target gene expression were compared after treatment with JA, OPDA, or phytoprostanes in mutants of the COI1/MYC2 pathway and in different TGA factor mutants. Inhibition of root growth by phytoprostanes was dependent on COI1 but independent of jasmonate biosynthesis. In contrast, phytoprostane-responsive gene expression was strongly dependent on TGA2, TGA5, and TGA6, but not dependent on COI1, MYC2, TGA1, and TGA4. Different mutant and overexpressing lines were used to determine individual contributions of TGA factors to cyclopentenone-responsive gene expression. Whereas OPDA-induced expression of the cytochrome P450 gene CYP81D11 was primarily regulated by TGA2 and TGA5, the glutathione S-transferase gene GST25 and the OPDA reductase gene OPR1 were regulated by TGA5 and TGA6, but less so by TGA2. These results support the model that phytoprostanes and OPDA regulate differently (i) growth responses, which are COI1 dependent but jasmonate independent; and (ii) lipid stress responses, which are strongly dependent on TGA2, TGA5, and TGA6. Identification of molecular components in cyclopentenone signalling provides an insight into novel oxylipin signal transduction pathways.}, language = {en} } @article{KleinertRollBaumgaertneretal.2012, author = {Kleinert, Stefan and Roll, Petra and Baumgaertner, Christian and Himsel, Andrea and Burkhardt, Harald and Mueller, Adelheid and Fleck, Martin and Feuchtenberger, Martin and Janett, Manfred and Tony, Hans-Peter}, title = {Renal Perfusion in Scleroderma Patients Assessed by Microbubble-Based Contrast-Enhanced Ultrasound}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75207}, year = {2012}, abstract = {Abstract: Objectives: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. Materials and Methodology: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE\%A) were calculated for different ROIs. Results: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. Conclusion: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media.}, subject = {Medizin}, language = {en} } @article{HarthKotzschHuetal.2010, author = {Harth, Stefan and Kotzsch, Alexander and Hu, Junli and Sebald, Walter and Mueller, Thomas D.}, title = {A Selection Fit Mechanism in BMP Receptor IA as a Possible Source for BMP Ligand-Receptor Promiscuity}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68497}, year = {2010}, abstract = {Background: Members of the TGF-b superfamily are characterized by a highly promiscuous ligand-receptor interaction as is readily apparent from the numeral discrepancy of only seven type I and five type II receptors available for more than 40 ligands. Structural and functional studies have been used to address the question of how specific signals can be deduced from a limited number of receptor combinations and to unravel the molecular mechanisms underlying the protein-protein recognition that allow such limited specificity. Principal Findings: In this study we have investigated how an antigen binding antibody fragment (Fab) raised against the extracellular domain of the BMP receptor type IA (BMPR-IA) recognizes the receptor's BMP-2 binding epitope and thereby neutralizes BMP-2 receptor activation. The crystal structure of the complex of the BMPR-IA ectodomain bound to the Fab AbD1556 revealed that the contact surface of BMPR-IA overlaps extensively with the contact surface for BMP-2 interaction. Although the structural epitopes of BMPR-IA to both binding partners coincides, the structures of BMPR-IA in the two complexes differ significantly. In contrast to the structural differences, alanine-scanning mutagenesis of BMPR-IA showed that the functional determinants for binding to the antibody and BMP-2 are almost identical. Conclusions: Comparing the structures of BMPR-IA bound to BMP-2 or bound to the Fab AbD1556 with the structure of unbound BMPR-IA shows that binding of BMPR-IA to its interaction partners follows a selection fit mechanism, possibly indicating that the ligand promiscuity of BMPR-IA is inherently encoded by structural adaptability. The functional and structural analysis of the BMPR-IA binding antibody AbD1556 mimicking the BMP-2 binding epitope may thus pave the way for the design of low-molecular weight synthetic receptor binders/inhibitors.}, subject = {Physiologische Chemie}, language = {en} } @article{MuellerLuettigMalyetal.2019, author = {Mueller, Stefan and L{\"u}ttig, Julian and Mal{\´y}, Pavel and Ji, Lei and Han, Jie and Moos, Michael and Marder, Todd B. and Bunz, Uwe H. F. and Dreuw, Andreas and Lambert, Christoph and Brixner, Tobias}, title = {Rapid multiple-quantum three-dimensional fluorescence spectroscopy disentangles quantum pathways}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-12602-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202529}, pages = {4735}, year = {2019}, abstract = {Coherent two-dimensional spectroscopy is a powerful tool for probing ultrafast quantum dynamics in complex systems. Several variants offer different types of information but typically require distinct beam geometries. Here we introduce population-based three-dimensional (3D) electronic spectroscopy and demonstrate the extraction of all fourth- and multiple sixth-order nonlinear signal contributions by employing 125-fold (1⨯5⨯5⨯5) phase cycling of a four-pulse sequence. Utilizing fluorescence detection and shot-to-shot pulse shaping in single-beam geometry, we obtain various 3D spectra of the dianion of TIPS-tetraazapentacene, a fluorophore with limited stability at ambient conditions. From this, we recover previously unknown characteristics of its electronic two-photon state. Rephasing and nonrephasing sixth-order contributions are measured without additional phasing that hampered previous attempts using noncollinear geometries. We systematically resolve all nonlinear signals from the same dataset that can be acquired in 8 min. The approach is generalizable to other incoherent observables such as external photoelectrons, photocurrents, or photoions.}, language = {en} } @article{SchaeblerAmatobiHornetal.2020, author = {Sch{\"a}bler, Stefan and Amatobi, Kelechi M. and Horn, Melanie and Rieger, Dirk and Helfrich‑F{\"o}rster, Charlotte and Mueller, Martin J. and Wegener, Christian and Fekete, Agnes}, title = {Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation}, series = {Cellular and Molecular Life Sciences}, volume = {77}, journal = {Cellular and Molecular Life Sciences}, issn = {1420-682X}, doi = {10.1007/s00018-019-03441-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232432}, pages = {4939-4956}, year = {2020}, abstract = {The fruit fly Drosophila is a prime model in circadian research, but still little is known about its circadian regulation of metabolism. Daily rhythmicity in levels of several metabolites has been found, but knowledge about hydrophobic metabolites is limited. We here compared metabolite levels including lipids between period\(^{01}\) (per\(^{01}\)) clock mutants and Canton-S wildtype (WT\(_{CS}\)) flies in an isogenic and non-isogenic background using LC-MS. In the non-isogenic background, metabo-lites with differing levels comprised essential amino acids, kynurenines, pterinates, glycero(phospho)lipids, and fatty acid esters. Notably, detectable diacylglycerols (DAG) and acylcarnitines (AC), involved in lipid metabolism, showed lower levels in per\(^{01}\) mutants. Most of these differences disappeared in the isogenic background, yet the level differences for AC as well as DAG were consistent for fly bodies. AC levels were dependent on the time of day in WTCS in phase with food consumption under LD conditions, while DAGs showed weak daily oscillations. Two short-chain ACs continued to cycle even in constant darkness. per\(^{01}\) mutants in LD showed no or very weak diel AC oscillations out of phase with feeding activity. The low levels of DAGs and ACs in per\(^{01}\) did not correlate with lower total food consumption, body mass or weight. Clock mutant flies showed higher sensitivity to starvation independent of their background-dependent activity level. Our results suggest that neither feeding, energy storage nor mobilisation is significantly affected in per\(^{01}\) mutants, but point towards impaired mitochondrial activity, supported by upregulation of the mitochondrial stress marker 4EBP in the clock mutants}, language = {en} } @unpublished{DietzschJayachandranMuelleretal.2023, author = {Dietzsch, Julia and Jayachandran, Ajay and Mueller, Stefan and H{\"o}bartner, Claudia and Brixner, Tobias}, title = {Excitonic coupling of RNA-templated merocyanine dimer studied by higher-order transient absorption spectroscopy}, series = {Chemical Communications}, journal = {Chemical Communications}, edition = {submitted version}, doi = {10.1039/D3CC02024J}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327772}, year = {2023}, abstract = {We report the synthesis and spectroscopic analysis of RNA containing the barbituric acid merocyanine rBAM2 as a nucleobase surrogate. Incorporation into RNA strands by solid-phase synthesis leads to fluorescence enhancement compared to the free chromophore. In addition, linear absorption studies show the formation of an excitonically coupled H-type dimer in the hybridized duplex. Ultrafast third- and fifth-order transient absorption spectroscopy of this non-fluorescent dimer suggests immediate (sub-200 fs) exciton transfer and annihilation due to the proximity of the rBAM2 units.}, language = {en} } @article{VollmerSaraviBreitenbuecheretal.2023, author = {Vollmer, Andreas and Saravi, Babak and Breitenbuecher, Niko and Mueller-Richter, Urs and Straub, Anton and Šimić, Luka and K{\"u}bler, Alexander and Vollmer, Michael and Gubik, Sebastian and Volland, Julian and Hartmann, Stefan and Brands, Roman C.}, title = {Realizing in-house algorithm-driven free fibula flap set up within 24 hours}, series = {Frontiers in Surgery}, volume = {10}, journal = {Frontiers in Surgery}, doi = {10.3389/fsurg.2023.1321217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-353945}, year = {2023}, abstract = {Objective: This study aims to critically evaluate the effectiveness and accuracy of a time safing and cost-efficient open-source algorithm for in-house planning of mandibular reconstructions using the free osteocutaneous fibula graft. The evaluation focuses on quantifying anatomical accuracy and assessing the impact on ischemia time. Methods: A pilot study was conducted, including patients who underwent in-house planned computer-aided design and manufacturing (CAD/CAM) of free fibula flaps between 2021 and 2023. Out of all patient cases, we included all with postoperative 3D imaging in the study. The study utilized open-source software tools for the planning step, and three-dimensional (3D) printing techniques. The Hausdorff distance and Dice coefficient metrics were used to evaluate the accuracy of the planning procedure. Results: The study assessed eight patients (five males and three females, mean age 61.75 ± 3.69 years) with different diagnoses such as osteoradionecrosis and oral squamous cell carcinoma. The average ischemia time was 68.38 ± 27.95 min. For the evaluation of preoperative planning vs. the postoperative outcome, the mean Hausdorff Distance was 1.22 ± 0.40. The Dice Coefficients yielded a mean of 0.77 ± 0.07, suggesting a satisfactory concordance between the planned and postoperative states. Dice Coefficient and Hausdorff Distance revealed significant correlations with ischemia time (Spearman's rho = -0.810, p = 0.015 and Spearman's rho = 0.762, p = 0.028, respectively). Linear regression models adjusting for disease type further substantiated these findings. Conclusions: The in-house planning algorithm not only achieved high anatomical accuracy, as reflected by the Dice Coefficients and Hausdorff Distance metrics, but this accuracy also exhibited a significant correlation with reduced ischemia time. This underlines the critical role of meticulous planning in surgical outcomes. Additionally, the algorithm's open-source nature renders it cost-efficient, easy to learn, and broadly applicable, offering promising avenues for enhancing both healthcare affordability and accessibility.}, language = {en} } @article{AmatobiOzbekUnalSchaebleretal.2023, author = {Amatobi, Kelechi M. and Ozbek-Unal, Ayten Gizem and Sch{\"a}bler, Stefan and Deppisch, Peter and Helfrich-F{\"o}rster, Charlotte and Mueller, Martin J. and Wegener, Christian and Fekete, Agnes}, title = {The circadian clock is required for rhythmic lipid transport in Drosophila in interaction with diet and photic condition}, series = {Journal of Lipid Research}, volume = {64}, journal = {Journal of Lipid Research}, number = {10}, doi = {10.1016/j.jlr.2023.100417}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349961}, pages = {100417}, year = {2023}, abstract = {Modern lifestyle is often at odds with endogenously driven rhythmicity, which can lead to circadian disruption and metabolic syndrome. One signature for circadian disruption is a reduced or altered metabolite cycling in the circulating tissue reflecting the current metabolic status. Drosophila is a well-established model in chronobiology, but day-time dependent variations of transport metabolites in the fly circulation are poorly characterized. Here, we sampled fly hemolymph throughout the day and analyzed diacylglycerols (DGs), phosphoethanolamines (PEs) and phosphocholines (PCs) using LC-MS. In wild-type flies kept on sugar-only medium under a light-dark cycle, all transport lipid species showed a synchronized bimodal oscillation pattern with maxima at the beginning and end of the light phase which were impaired in period01 clock mutants. In wild-type flies under constant dark conditions, the oscillation became monophasic with a maximum in the middle of the subjective day. In strong support of clock-driven oscillations, levels of the targeted lipids peaked once in the middle of the light phase under time-restricted feeding independent of the time of food intake. When wild-type flies were reared on full standard medium, the rhythmic alterations of hemolymph lipid levels were greatly attenuated. Our data suggest that the circadian clock aligns daily oscillations of DGs, PEs, and PCs in the hemolymph to the anabolic siesta phase, with a strong influence of light on phase and modality.}, language = {en} }