@article{HaederSchaeubleGehlenetal.2023, author = {H{\"a}der, Antje and Sch{\"a}uble, Sascha and Gehlen, Jan and Thielemann, Nadja and Buerfent, Benedikt C. and Sch{\"u}ller, Vitalia and Hess, Timo and Wolf, Thomas and Schr{\"o}der, Julia and Weber, Michael and H{\"u}nniger, Kerstin and L{\"o}ffler, J{\"u}rgen and Vylkova, Slavena and Panagiotou, Gianni and Schumacher, Johannes and Kurzai, Oliver}, title = {Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-38994-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357441}, year = {2023}, abstract = {Innate immune responses vary by pathogen and host genetics. We analyze quantitative trait loci (eQTLs) and transcriptomes of monocytes from 215 individuals stimulated by fungal, Gram-negative or Gram-positive bacterial pathogens. We identify conserved monocyte responses to bacterial pathogens and a distinct antifungal response. These include 745 response eQTLs (reQTLs) and corresponding genes with pathogen-specific effects, which we find first in samples of male donors and subsequently confirm for selected reQTLs in females. reQTLs affect predominantly upregulated genes that regulate immune response via e.g., NOD-like, C-type lectin, Toll-like and complement receptor-signaling pathways. Hence, reQTLs provide a functional explanation for individual differences in innate response patterns. Our identified reQTLs are also associated with cancer, autoimmunity, inflammatory and infectious diseases as shown by external genome-wide association studies. Thus, reQTLs help to explain interindividual variation in immune response to infection and provide candidate genes for variants associated with a range of diseases.}, language = {en} } @article{GriebelSegebarthSteinetal.2023, author = {Griebel, Matthias and Segebarth, Dennis and Stein, Nikolai and Schukraft, Nina and Tovote, Philip and Blum, Robert and Flath, Christoph M.}, title = {Deep learning-enabled segmentation of ambiguous bioimages with deepflash2}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-36960-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357286}, year = {2023}, abstract = {Bioimages frequently exhibit low signal-to-noise ratios due to experimental conditions, specimen characteristics, and imaging trade-offs. Reliable segmentation of such ambiguous images is difficult and laborious. Here we introduce deepflash2, a deep learning-enabled segmentation tool for bioimage analysis. The tool addresses typical challenges that may arise during the training, evaluation, and application of deep learning models on ambiguous data. The tool's training and evaluation pipeline uses multiple expert annotations and deep model ensembles to achieve accurate results. The application pipeline supports various use-cases for expert annotations and includes a quality assurance mechanism in the form of uncertainty measures. Benchmarked against other tools, deepflash2 offers both high predictive accuracy and efficient computational resource usage. The tool is built upon established deep learning libraries and enables sharing of trained model ensembles with the research community. deepflash2 aims to simplify the integration of deep learning into bioimage analysis projects while improving accuracy and reliability.}, language = {en} } @article{HaerterichMatlerDewhurstetal.2023, author = {H{\"a}rterich, Marcel and Matler, Alexander and Dewhurst, Rian D. and Sachs, Andreas and Oppel, Kai and Stoy, Andreas and Braunschweig, Holger}, title = {A step-for-step main-group replica of the Fischer carbene synthesis at a borylene carbonyl}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-36251-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357270}, year = {2023}, abstract = {The Fischer carbene synthesis, involving the conversion of a transition metal (TM)-bound CO ligand to a carbene ligand of the form [=C(OR')R] (R, R' = organyl groups), is one of the seminal reactions in the history of organometallic chemistry. Carbonyl complexes of p-block elements, of the form [E(CO)n] (E = main-group fragment), are much less abundant than their TM cousins; this scarcity and the general instability of low-valent p-block species means that replicating the historical reactions of TM carbonyls is often very difficult. Here we present a step-for-step replica of the Fischer carbene synthesis at a borylene carbonyl involving nucleophilic attack at the carbonyl carbon followed by electrophilic quenching at the resultant acylate oxygen atom. These reactions provide borylene acylates and alkoxy-/silyloxy-substituted alkylideneboranes, main-group analogues of the archetypal transition metal acylate and Fischer carbene families, respectively. When either the incoming electrophile or the boron center has a modest steric profile, the electrophile instead attacks at the boron atom, leading to carbene-stabilized acylboranes - boron analogues of the well-known transition metal acyl complexes. These results constitute faithful main-group replicas of a number of historical organometallic processes and pave the way to further advances in the field of main-group metallomimetics.}, language = {en} } @article{WehShoyamaWuerthner2023, author = {Weh, Manuel and Shoyama, Kazutaka and W{\"u}rthner, Frank}, title = {Preferential molecular recognition of heterochiral guests within a cyclophane receptor}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-35851-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357750}, year = {2023}, abstract = {The discrimination of enantiomers by natural receptors is a well-established phenomenon. In contrast the number of synthetic receptors with the capability for enantioselective molecular recognition of chiral substrates is scarce and for chiral cyclophanes indicative for a preferential binding of homochiral guests. Here we introduce a cyclophane composed of two homochiral core-twisted perylene bisimide (PBI) units connected by p-xylylene spacers and demonstrate its preference for the complexation of [5]helicene of opposite helicity compared to the PBI units of the host. The pronounced enantio-differentiation of this molecular receptor for heterochiral guests can be utilized for the enrichment of the P-PBI-M-helicene-P-PBI epimeric bimolecular complex. Our experimental results are supported by DFT calculations, which reveal that the sterically demanding bay substituents attached to the PBI chromophores disturb the helical shape match of the perylene core and homochiral substrates and thereby enforce the formation of syndiotactic host-guest complex structures. Hence, the most efficient substrate binding is observed for those aromatic guests, e. g. perylene, [4]helicene, phenanthrene and biphenyl, that can easily adapt in non-planar axially chiral conformations due to their inherent conformational flexibility. In all cases the induced chirality for the guest is opposed to those of the embedding PBI units, leading to heterochiral host-guest structures.}, language = {en} } @article{NishidaXavierdaSilvaSchulteNunesAlvesetal.2023, author = {Nishida Xavier da Silva, Thamara and Schulte, Clemens and Nunes Alves, Ariane and Maric, Hans Michael and Friedmann Angeli, Jos{\´e} Pedro}, title = {Molecular characterization of AIFM2/FSP1 inhibition by iFSP1-like molecules}, series = {Cell Death \& Disease}, volume = {14}, journal = {Cell Death \& Disease}, doi = {10.1038/s41419-023-05787-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357943}, year = {2023}, abstract = {Ferroptosis is a form of cell death characterized by phospholipid peroxidation, where numerous studies have suggested that the induction of ferroptosis is a therapeutic strategy to target therapy refractory cancer entities. Ferroptosis suppressor protein 1 (FSP1), an NAD(P)H-ubiquinone reductase, is a key determinant of ferroptosis vulnerability, and its pharmacological inhibition was shown to strongly sensitize cancer cells to ferroptosis. A first generation of FSP1 inhibitors, exemplified by the small molecule iFSP1, has been reported; however, the molecular mechanisms underlying inhibition have not been characterized in detail. In this study, we explore the species-specific inhibition of iFSP1 on the human isoform to gain insights into its mechanism of action. Using a combination of cellular, biochemical, and computational methods, we establish a critical contribution of a species-specific aromatic architecture that is essential for target engagement. The results described here provide valuable insights for the rational development of second-generation FSP1 inhibitors combined with a tracer for screening the druggable pocket. In addition, we pose a cautionary notice for using iFSP1 in animal models, specifically murine models.}, language = {en} } @article{MaichlKirnerBecketal.2023, author = {Maichl, Daniela Simone and Kirner, Julius Arthur and Beck, Susanne and Cheng, Wen-Hui and Krug, Melanie and Kuric, Martin and Ade, Carsten Patrick and Bischler, Thorsten and Jakob, Franz and Hose, Dirk and Seckinger, Anja and Ebert, Regina and Jundt, Franziska}, title = {Identification of NOTCH-driven matrisome-associated genes as prognostic indicators of multiple myeloma patient survival}, series = {Blood Cancer Journal}, volume = {13}, journal = {Blood Cancer Journal}, doi = {10.1038/s41408-023-00907-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357598}, year = {2023}, abstract = {No abstract available.}, language = {en} } @article{IpWischhusen2023, author = {Ip, Chi Wang and Wischhusen, J{\"o}rg}, title = {Versatile guardians: regenerative regulatory T cells in Parkinson's disease rodent models}, series = {Signal Transduction and Targeted Therapy}, volume = {8}, journal = {Signal Transduction and Targeted Therapy}, doi = {10.1038/s41392-023-01681-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357674}, year = {2023}, abstract = {No abstract available.}, language = {en} } @article{RodriguezRozadaFrantzTovote2023, author = {Rodriguez-Rozada, Silvia and Frantz, Stefan and Tovote, Philip}, title = {Cardiac optogenetics: regulating brain states via the heart}, series = {Signal Transduction and Targeted Therapy}, volume = {8}, journal = {Signal Transduction and Targeted Therapy}, doi = {10.1038/s41392-023-01582-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357625}, year = {2023}, abstract = {No abstract available.}, language = {en} } @article{KlimmBraeuKoenigetal.2024, author = {Klimm, Fabian S. and Br{\"a}u, Markus and K{\"o}nig, Sebastian and Mandery, Klaus and Sommer, Carolin and Zhang, Jie and Krauss, Jochen}, title = {Importance of habitat area, quality and landscape context for heteropteran diversity in shrub ecotones}, series = {Landscape Ecology}, volume = {39}, journal = {Landscape Ecology}, issn = {0921-2973}, doi = {10.1007/s10980-024-01798-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358106}, year = {2024}, abstract = {Context Habitat loss and degradation impose serious threats on biodiversity. However, not all habitats receive the attention commensurate with their ecological importance. Shrub ecotones (successional stages between grasslands and forests) can be highly species-diverse but are often restricted to small areas as prevalent management practices either promote open grassland or forest habitats, threatening the effective conservation of ecotone species. Objectives In this study, we assessed the importance of habitat and landscape features of shrub ecotones for the rarely studied true bugs (Heteroptera), a functionally diverse taxon that comprises highly specialized species and broad generalists. Methods True bugs were sampled with a beating tray in 118 spatially independent shrub ecotones in a region of 45,000 square kilometers in Germany. In addition to habitat area and landscape context, we used a hedge index to evaluate habitat quality. Results Shrub ecotones in open habitats harbored a greater species richness and abundance compared to shaded ones in later seral stages, and species composition differed. Richness and abundance were positively affected by increasing habitat area and quality, whereas an increase in the proportion of semi-natural habitats within 1 km only enhanced richness. While feeding and habitat specialists were more sensitive to habitat area reduction than generalists, this was not the case for weak dispersers and carnivores. Conclusions Our findings emphasize the importance of large and high-quality ecotones that form a patchy mosaic of shrubs and herbaceous plants. Such ecotones can benefit both grassland species and species depending on woody plants. Conservation authorities should balance between promoting shrubs and keeping such habitats open to maximize species diversity.}, language = {en} } @article{OPUS4-22781, title = {Long-term monitoring of the ANTARES optical module efficiencies using \(^{40}\)K decays in sea water}, series = {European Physical Journal C}, volume = {78}, journal = {European Physical Journal C}, organization = {The ANTARES Collaboration}, doi = {10.1140/epjc/s10052-018-6132-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227815}, pages = {1-8}, year = {2018}, abstract = {Cherenkov light induced by radioactive decay products is one of the major sources of background light for deep-sea neutrino telescopes such as ANTARES. These decays are at the same time a powerful calibration source. Using data collected by the ANTARES neutrino telescope from mid 2008 to 2017, the time evolution of the photon detection efficiency of optical modules is studied. A modest loss of only 20\% in 9 years is observed. The relative time calibration between adjacent modules is derived as well.}, language = {en} } @article{RennerOttoKuebleretal.2023, author = {Renner, Tobias and Otto, Paul and K{\"u}bler, Alexander C. and H{\"o}lscher-Doht, Stefanie and Gbureck, Uwe}, title = {Novel adhesive mineral-organic bone cements based on phosphoserine and magnesium phosphates or oxides}, series = {Journal of Materials Science: Materials in Medicine}, volume = {34}, journal = {Journal of Materials Science: Materials in Medicine}, doi = {10.1007/s10856-023-06714-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357342}, year = {2023}, abstract = {Present surgical situations require a bone adhesive which has not yet been developed for use in clinical applications. Recently, phosphoserine modified cements (PMC) based on mixtures of o-phosphoserine (OPLS) and calcium phosphates, such as tetracalcium phosphate (TTCP) or α-tricalcium phosphate (α-TCP) as well as chelate setting magnesium phosphate cements have gained increasing popularity for their use as mineral bone adhesives. Here, we investigated new mineral-organic bone cements based on phosphoserine and magnesium phosphates or oxides, which possess excellent adhesive properties. These were analyzed by X-ray diffraction, Fourier infrared spectroscopy and electron microscopy and subjected to mechanical tests to determine the bond strength to bone after ageing at physiological conditions. The novel biomineral adhesives demonstrate excellent bond strength to bone with approximately 6.6-7.3 MPa under shear load. The adhesives are also promising due to their cohesive failure pattern and ductile character. In this context, the new adhesive cements are superior to currently prevailing bone adhesives. Future efforts on bone adhesives made from phosphoserine and Mg2+ appear to be very worthwhile.}, language = {en} } @article{AlbertAndreAnghinolfietal.2019, author = {Albert, A. and Andr{\´e}, M. and Anghinolfi, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Aublin, J. and Avgitas, T. and Baret, B. and Barrios-Mart{\´i}t, J. and Basa, S. and Belhorma, B. and Bertin, V. and Biagi, S. and Bormuth, R. and Boumaaza, J and Bourret, S. and Bouwhuis, M. C. and Br{\^a}nzas, H. and Bruijn, R. and Brunner, J. and Busto, J. and Capone, A. and Caramete, L. and Carr, J. and Celli, S. and Chabab, M. and Cherkaoui El Moursli, R. and Chiarusi, T. and Circella, M. and Coelho, J. A. B. and Coleiro, A. and Colomer, M and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and D{\´i}az, A. F. and Deschamps, A. and Distefano, C. and Di Palma, I. and Domi, A. and Donzaud, C. and Dornic, D. and Drouhin, D. and Eberl, T. and El Bojaddaini, I. and El Khayati, N. and Els{\"a}sser, D. and Enzenh{\"o}fer, A. and Ettahiri, A. and Fassi, F. and Felis, I. and Fermani, P. and Ferrara, G. and Fusco, L. A. and Gay, P. and Glotin, H. and Gr{\´e}goire, T. and Gracia Ruiz, R. and Graf, K. and Hallmann, S. and van Haren, H. and Heijboer, A. J. and Hello, Y. and Hern{\´a}ndez-Rey, J. J. and H{\"o}ßl, J. and Hofest{\"a}dt, J. and Illuminati, G. and de Jong, M. and Jongen, M. and Kadler, M. and Kalekin, O. and Katz, U. and Khan-Chowdhury, N. R. and Kouchner, A. and Kreter, M. and Kreykenbohm, I. and Kulikovskiy, V. and Lachaud, C. and Lahmann, R. and Lef{\`e}vre, D. and Leonora, E. and Levi, G. and Lotze, M. and Loucatos, S. and Marcelin, M. and Margiotta, A. and Marinelli, A. and Mart{\´i}nez-Mora, J. A. and Mele, R. and Melis, K. and Migliozzi, P. and Moussa, A. and Navas, S. and Nezri, E. and Nu{\~n}ez, A. and Organokov, M. and Pavalas, G. E. and Pellegrino, C. and Piattelli, P. and Popa, V. and Pradier, T. and Quinn, L. and Racca, C. and Randazzo, N. and Riccobene, G. and S{\´a}nchez-Losa, A. and Salda{\~n}a, M. and Salvadori, I. and Samtleben, D. F. E. and Sanguineti, M. and Sapienza, P. and Sch{\"u}ssler, F. and Spurio, M. and Stolarczyk, Th. and Taiuti, M. and Tayalati, Y. and Trovato, A. and Vallage, B. and Van Elewyck, V. and Versari, F. and Vivolo, D. and Wilms, J. and Zaborov, D. and Zornoza, J. D. and Z{\´u}{\~n}iga, J.}, title = {The cosmic ray shadow of the Moon observed with the ANTARES neutrino telescope}, series = {European Physical Journal C}, volume = {78}, journal = {European Physical Journal C}, doi = {10.1140/epjc/s10052-018-6451-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227802}, pages = {1-9}, year = {2019}, abstract = {One of the main objectives of the ANTARES telescope is the search for point- like neutrino sources. Both the pointing accuracy and the angular resolution of the detector are important in this context and a reliableway to evaluate this performance is needed. In order to measure the pointing accuracy of the detector, one possibility is to study the shadow of the Moon, i. e. the deficit of the atmospheric muon flux from the direction of the Moon induced by the absorption of cosmic rays. Analysing the data taken between 2007 and 2016, theMoon shadow is observed with 3.5s statistical significance. The detector angular resolution for downwardgoing muons is 0.73. +/- 0.14.. The resulting pointing performance is consistent with the expectations. An independent check of the telescope pointing accuracy is realised with the data collected by a shower array detector onboard of a ship temporarily moving around the ANTARES location.}, language = {en} } @article{ReppenhagenBeckerKugleretal.2023, author = {Reppenhagen, Stephan and Becker, Roland and Kugler, Andreas and John, Dominik and Kopf, Sebastian and Anetzberger, Hermann}, title = {Hand dominance is not of significance in performing fundamental arthroscopic skills simulation training tasks}, series = {Arthroscopy, Sports Medicine, and Rehabilitation}, volume = {5}, journal = {Arthroscopy, Sports Medicine, and Rehabilitation}, number = {5}, issn = {2666-061X}, doi = {10.1016/j.asmr.2023.100767}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350432}, year = {2023}, abstract = {Purpose To compare the performance of the dominant and nondominant hand during fundamental arthroscopic simulator training. Methods Surgical trainees who participated in a 2-day simulator training course between 2021 and 2023 were classified, according to their arthroscopic experience in beginners and competents. Only right-handed individuals with complete data sets were included in the study. Ambidexterity was trained using a box trainer (Fundamentals of Arthroscopic Surgery Training, Virtamed AG, Schlieren, Switzerland).Two tasks, periscoping for learning camera guidance and triangulation for additional instrument handling, were performed 4 times with the camera in the dominant hand and then in the nondominant hand. For each task, exercise time, camera path length, and instrument path length were recorded and analyzed. Results Out of 94 participants 74 right-handed individuals (22 females, 52 males) were classified to novices (n = 43, less than 10 independently performed arthroscopies) and competents (n = 31, more than 10 independently performed arthroscopies). Competents performed significantly better than novices. No significant difference was found after changing the guiding hand for the camera from the dominant to the nondominant hand regarding the camera path length and the instrument path length. Notably, tasks were performed even faster when using the camera in the nondominant hand. Conclusions Our data demonstrate that the learned manual skills during basic arthroscopic training are quickly transferred to the contralateral side. In consequence, additional fundamental skills training for camera guidance and instrument handling of the nondominant hand are not necessary. Clinical Relevance For skillful arthroscopy, camera guidance and instrument handing must be equally mastered with both hands. It is important to understand how hand dominance may affect learning during arthroscopic simulator training.}, language = {en} } @article{JaenschEvdokimovEgenolfetal.2024, author = {J{\"a}nsch, Sarah and Evdokimov, Dimitar and Egenolf, Nadine and Meyer zu Altenschildesche, Caren and Kreß, Luisa and {\"U}{\c{c}}eyler, Nurcan}, title = {Distinguishing fibromyalgia syndrome from small fiber neuropathy: a clinical guide}, series = {Pain Reports}, volume = {9}, journal = {Pain Reports}, number = {1}, doi = {10.1097/PR9.0000000000001136}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350306}, year = {2024}, abstract = {Introduction: Fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) are distinct pain conditions that share commonalities and may be challenging as for differential diagnosis. Objective: To comprehensively investigate clinical characteristics of women with FMS and SFN to determine clinically applicable parameters for differentiation. Methods: We retrospectively analyzed medical records of 158 women with FMS and 53 with SFN focusing on pain-specific medical and family history, accompanying symptoms, additional diseases, and treatment. We investigated data obtained using standardized pain, depression, and anxiety questionnaires. We further analyzed test results and findings obtained in standardized small fiber tests. Results: FMS patients were on average ten years younger at symptom onset, described higher pain intensities requiring frequent change of pharmaceutics, and reported generalized pain compared to SFN. Pain in FMS was accompanied by irritable bowel or sleep disturbances, and in SFN by paresthesias, numbness, and impaired glucose metabolism (P < 0.01 each). Family history was informative for chronic pain and affective disorders in FMS (P < 0.001) and for neurological disorders in SFN patients (P < 0.001). Small fiber pathology in terms of skin denervation and/or thermal sensory threshold elevation was present in 110/158 (69.7 \%) FMS patients and 39/53 (73.6 \%) SFN patients. FMS patients mainly showed proximally reduced skin innervation and higher corneal nerve branch densities (p<0.001) whereas SFN patients were characterized by reduced cold detection and prolonged electrical A-delta conduction latencies (P < 0.05). Conclusions: Our data show that FMS and SFN differ substantially. Detailed pain, drug and family history, investigating blood glucose metabolism, and applying differential small fiber tests may help to improve diagnostic differentiation and targeted therapy.}, language = {en} } @article{BreyerGruenerKleinetal.2024, author = {Breyer, Maximilian and Gr{\"u}ner, Julia and Klein, Alexandra and Finke, Laura and Klug, Katharina and Sauer, Markus and {\"U}{\c{c}}eyler, Nurcan}, title = {\(In\) \(vitro\) characterization of cells derived from a patient with the GLA variant c.376A>G (p.S126G) highlights a non-pathogenic role in Fabry disease}, series = {Molecular Genetics and Metabolism Reports}, volume = {38}, journal = {Molecular Genetics and Metabolism Reports}, issn = {22144269}, doi = {10.1016/j.ymgmr.2023.101029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350295}, year = {2024}, abstract = {Highlights • The GLA variant S126G is not associated with Fabry symptoms in the presented case • S126G has no effect on α-GAL A activity or Gb3 levels in this patient • S126G sensory neurons show no electrophysiological abnormalities Abstract Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene GLA. Variants of unknown significance (VUS) are frequently found in GLA and challenge clinical management. Here, we investigated a 49-year old man with cryptogenic lacunar cerebral stroke and the chance finding of the VUS S126G, who was sent to our center for diagnosis and initiation of a costly and life-long FD-specific treatment. We combined clinical examination with in vitro investigations of dermal fibroblasts (HDF), induced pluripotent stem cells (iPSC), and iPSC-derived sensory neurons. We analyzed α-GAL A activity in iPSC, Gb3 accumulation in all three cell types, and action potential firing in sensory neurons. Neurological examination and small nerve fiber assessment was normal except for reduced distal skin innervation. S126G iPSC showed normal α-GAL A activity compared to controls and no Gb3 deposits were found in all three cell types. Baseline electrophysiological characteristics of S126G neurons showed no difference compared to healthy controls as investigated by patch-clamp recordings. We pioneer multi-level cellular characterization of the VUS S126G using three cell types derived from a patient and provide further evidence for the benign nature of S126G in GLA, which is of great importance in the management of such cases in clinical practice.}, language = {en} } @article{BinderLangePozzietal.2023, author = {Binder, Tobias and Lange, Florian and Pozzi, Nicol{\`o} and Musacchio, Thomas and Daniels, Christine and Odorfer, Thorsten and Fricke, Patrick and Matthies, Cordula and Volkmann, Jens and Capetian, Philipp}, title = {Feasibility of local field potential-guided programming for deep brain stimulation in Parkinson's disease: a comparison with clinical and neuro-imaging guided approaches in a randomized, controlled pilot trial}, series = {Brain Stimulation}, volume = {16}, journal = {Brain Stimulation}, number = {5}, doi = {10.1016/j.brs.2023.08.017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350280}, pages = {1243-1251}, year = {2023}, abstract = {Highlights • Beta-Guided programming is an innovative approach that may streamline the programming process for PD patients with STN DBS. • While preliminary findings from our study suggest that Beta Titration may potentially mitigate STN overstimulation and enhance symptom control, • Our results demonstrate that beta-guided programming significantly reduces programming time, suggesting it could be efficiently integrated into routine clinical practice using a commercially available patient programmer. Background Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson's disease (PD). Clinical outcomes after DBS can be limited by poor programming, which remains a clinically driven, lengthy and iterative process. Electrophysiological recordings in PD patients undergoing STN-DBS have shown an association between STN spectral power in the beta frequency band (beta power) and the severity of clinical symptoms. New commercially-available DBS devices now enable the recording of STN beta oscillations in chronically-implanted PD patients, thereby allowing investigation into the use of beta power as a biomarker for DBS programming. Objective To determine the potential advantages of beta-guided DBS programming over clinically and image-guided programming in terms of clinical efficacy and programming time. Methods We conducted a randomized, blinded, three-arm, crossover clinical trial in eight Parkinson's patients with STN-DBS who were evaluated three months after DBS surgery. We compared clinical efficacy and time required for each DBS programming paradigm, as well as DBS parameters and total energy delivered between the three strategies (beta-, clinically- and image-guided). Results All three programming methods showed similar clinical efficacy, but the time needed for programming was significantly shorter for beta- and image-guided programming compared to clinically-guided programming (p < 0.001). Conclusion Beta-guided programming may be a useful and more efficient approach to DBS programming in Parkinson's patients with STN-DBS. It takes significantly less time to program than traditional clinically-based programming, while providing similar symptom control. In addition, it is readily available within the clinical DBS programmer, making it a valuable tool for improving current clinical practice.}, language = {en} } @article{WiesslerTalucciPiroetal.2024, author = {Wiessler, Anna-Lena and Talucci, Ivan and Piro, Inken and Seefried, Sabine and H{\"o}rlin, Verena and Baykan, Bet{\"u}l B. and T{\"u}z{\"u}n, Erdem and Schaefer, Natascha and Maric, Hans M. and Sommer, Claudia and Villmann, Carmen}, title = {Glycine receptor β-targeting autoantibodies contribute to the pathology of autoimmune diseases}, series = {Neurology: Neuroimmunology \& Neuroinflammation}, volume = {11}, journal = {Neurology: Neuroimmunology \& Neuroinflammation}, number = {2}, doi = {10.1212/NXI.0000000000200187}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349958}, year = {2024}, abstract = {Background and Objectives Stiff-person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM) are rare neurologic disorders of the CNS. Until now, exclusive GlyRα subunit-binding autoantibodies with subsequent changes in function and surface numbers were reported. GlyR autoantibodies have also been described in patients with focal epilepsy. Autoimmune reactivity against the GlyRβ subunits has not yet been shown. Autoantibodies against GlyRα1 target the large extracellular N-terminal domain. This domain shares a high degree of sequence homology with GlyRβ making it not unlikely that GlyRβ-specific autoantibody (aAb) exist and contribute to the disease pathology. Methods In this study, we investigated serum samples from 58 patients for aAb specifically detecting GlyRβ. Studies in microarray format, cell-based assays, and primary spinal cord neurons and spinal cord tissue immunohistochemistry were performed to determine specific GlyRβ binding and define aAb binding to distinct protein regions. Preadsorption approaches of aAbs using living cells and the purified extracellular receptor domain were further used. Finally, functional consequences for inhibitory neurotransmission upon GlyRβ aAb binding were resolved by whole-cell patch-clamp recordings. Results Among 58 samples investigated, cell-based assays, tissue analysis, and preadsorption approaches revealed 2 patients with high specificity for GlyRβ aAb. Quantitative protein cluster analysis demonstrated aAb binding to synaptic GlyRβ colocalized with the scaffold protein gephyrin independent of the presence of GlyRα1. At the functional level, binding of GlyRβ aAb from both patients to its target impair glycine efficacy. Discussion Our study establishes GlyRβ as novel target of aAb in patients with SPS/PERM. In contrast to exclusively GlyRα1-positive sera, which alter glycine potency, aAbs against GlyRβ impair receptor efficacy for the neurotransmitter glycine. Imaging and functional analyses showed that GlyRβ aAbs antagonize inhibitory neurotransmission by affecting receptor function rather than localization.}, language = {en} } @article{DrehmannMilanosSchaeferetal.2023, author = {Drehmann, Paul and Milanos, Sinem and Schaefer, Natascha and Kasaragod, Vikram Babu and Herterich, Sarah and Holzbach-Eberle, Ulrike and Harvey, Robert J. and Villmann, Carmen}, title = {Dual role of dysfunctional Asc-1 transporter in distinct human pathologies, human startle disease, and developmental delay}, series = {eNeuro}, volume = {10}, journal = {eNeuro}, number = {11}, doi = {10.1523/ENEURO.0263-23.2023}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349947}, year = {2023}, abstract = {Human startle disease is associated with mutations in distinct genes encoding glycine receptors, transporters or interacting proteins at glycinergic synapses in spinal cord and brainstem. However, a significant number of diagnosed patients does not carry a mutation in the common genes GLRA1, GLRB, and SLC6A5. Recently, studies on solute carrier 7 subfamily 10 (SLC7A10; Asc-1, alanine-serine-cysteine transporter) knock-out (KO) mice displaying a startle disease-like phenotype hypothesized that this transporter might represent a novel candidate for human startle disease. Here, we screened 51 patients from our patient cohort negative for the common genes and found three exonic (one missense, two synonymous), seven intronic, and single nucleotide changes in the 5′ and 3′ untranslated regions (UTRs) in Asc-1. The identified missense mutation Asc-1\(^{G307R}\) from a patient with startle disease and developmental delay was investigated in functional studies. At the molecular level, the mutation Asc-1\(^{G307R}\) did not interfere with cell-surface expression, but disrupted glycine uptake. Substitution of glycine at position 307 to other amino acids, e.g., to alanine or tryptophan did not affect trafficking or glycine transport. By contrast, G307K disrupted glycine transport similar to the G307R mutation found in the patient. Structurally, the disrupted function in variants carrying positively charged residues can be explained by local structural rearrangements because of the large positively charged side chain. Thus, our data suggest that SLC7A10 may represent a rare but novel gene associated with human startle disease and developmental delay.}, language = {en} } @article{VollmerNaglerHoerneretal.2023, author = {Vollmer, Andreas and Nagler, Simon and H{\"o}rner, Marius and Hartmann, Stefan and Brands, Roman C. and Breitenb{\"u}cher, Niko and Straub, Anton and K{\"u}bler, Alexander and Vollmer, Michael and Gubik, Sebastian and Lang, Gernot and Wollborn, Jakob and Saravi, Babak}, title = {Performance of artificial intelligence-based algorithms to predict prolonged length of stay after head and neck cancer surgery}, series = {Heliyon}, volume = {9}, journal = {Heliyon}, number = {11}, issn = {2405-8440}, doi = {10.1016/j.heliyon.2023.e20752}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350416}, year = {2023}, abstract = {Background Medical resource management can be improved by assessing the likelihood of prolonged length of stay (LOS) for head and neck cancer surgery patients. The objective of this study was to develop predictive models that could be used to determine whether a patient's LOS after cancer surgery falls within the normal range of the cohort. Methods We conducted a retrospective analysis of a dataset consisting of 300 consecutive patients who underwent head and neck cancer surgery between 2017 and 2022 at a single university medical center. Prolonged LOS was defined as LOS exceeding the 75th percentile of the cohort. Feature importance analysis was performed to evaluate the most important predictors for prolonged LOS. We then constructed 7 machine learning and deep learning algorithms for the prediction modeling of prolonged LOS. Results The algorithms reached accuracy values of 75.40 (radial basis function neural network) to 97.92 (Random Trees) for the training set and 64.90 (multilayer perceptron neural network) to 84.14 (Random Trees) for the testing set. The leading parameters predicting prolonged LOS were operation time, ischemia time, the graft used, the ASA score, the intensive care stay, and the pathological stages. The results revealed that patients who had a higher number of harvested lymph nodes (LN) had a lower probability of recurrence but also a greater LOS. However, patients with prolonged LOS were also at greater risk of recurrence, particularly when fewer (LN) were extracted. Further, LOS was more strongly correlated with the overall number of extracted lymph nodes than with the number of positive lymph nodes or the ratio of positive to overall extracted lymph nodes, indicating that particularly unnecessary lymph node extraction might be associated with prolonged LOS. Conclusions The results emphasize the need for a closer follow-up of patients who experience prolonged LOS. Prospective trials are warranted to validate the present results.}, language = {en} } @article{HruschkaAppel2023, author = {Hruschka, Timon M. J. and Appel, Markus}, title = {Learning about informal fallacies and the detection of fake news: an experimental intervention}, series = {PLoS One}, volume = {18}, journal = {PLoS One}, number = {3}, issn = {1932-6203}, doi = {10.1371/journal.pone.0283238}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350404}, year = {2023}, abstract = {The philosophical concept of informal fallacies-arguments that fail to provide sufficient support for a claim-is introduced and connected to the topic of fake news detection. We assumed that the ability to identify informal fallacies can be trained and that this ability enables individuals to better distinguish between fake news and real news. We tested these assumptions in a two-group between-participants experiment (N = 116). The two groups participated in a 30-minute-long text-based learning intervention: either about informal fallacies or about fake news. Learning about informal fallacies enhanced participants' ability to identify fallacious arguments one week later. Furthermore, the ability to identify fallacious arguments was associated with a better discernment between real news and fake news. Participants in the informal fallacy intervention group and the fake news intervention group performed equally well on the news discernment task. The contribution of (identifying) informal fallacies for research and practice is discussed.}, language = {en} }