@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{TrifaultMamontovaCossaetal.2024, author = {Trifault, Barbara and Mamontova, Victoria and Cossa, Giacomo and Ganskih, Sabina and Wei, Yuanjie and Hofstetter, Julia and Bhandare, Pranjali and Baluapuri, Apoorva and Nieto, Blanca and Solvie, Daniel and Ade, Carsten P. and Gallant, Peter and Wolf, Elmar and Larsen, Dorthe H. and Munschauer, Mathias and Burger, Kaspar}, title = {Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts}, series = {Nucleic Acids Research}, volume = {52}, journal = {Nucleic Acids Research}, number = {6}, doi = {10.1093/nar/gkae022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350208}, pages = {3050-3068}, year = {2024}, abstract = {RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54\(^{nrb}\) marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells. Such transcripts originate from distinct nucleolar intergenic spacer regions and form DNA-RNA hybrids to tether NONO to the nucleolus in an RNA recognition motif 1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.}, language = {en} } @article{HofstetterOgunleyeKutschkeetal.2024, author = {Hofstetter, Julia and Ogunleye, Ayoola and Kutschke, Andr{\´e} and Buchholz, Lisa Marie and Wolf, Elmar and Raabe, Thomas and Gallant, Peter}, title = {Spt5 interacts genetically with Myc and is limiting for brain tumor growth in Drosophila}, series = {Life Science Alliance}, volume = {7}, journal = {Life Science Alliance}, number = {1}, issn = {2575-1077}, doi = {10.26508/lsa.202302130}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350197}, year = {2024}, abstract = {The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use Drosophila to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells. During later development, Spt5-knockdown has no detectable consequences on its own, but strongly enhances eye defects caused by Myc overexpression. Similarly, Spt5-knockdown in larval type 2 neuroblasts has only mild effects on brain development and survival of control flies, but dramatically shrinks the volumes of experimentally induced neuroblast tumors and significantly extends the lifespan of tumor-bearing animals. This beneficial effect is still observed when Spt5 is knocked down systemically and after tumor initiation, highlighting SPT5 as a potential drug target in human oncology.}, language = {en} } @article{ThenPohlmannRother2024, author = {Then, Daniel and Pohlmann-Rother, Sanna}, title = {Adaptivity in the inclusive transition to school}, series = {Frontiers in Education}, volume = {8}, journal = {Frontiers in Education}, issn = {2504-284X}, doi = {10.3389/feduc.2023.1304918}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-354256}, year = {2024}, abstract = {The transition to school is a key juncture in an individual's educational trajectory, with far-reaching effects on the development of children and their families. Successful transitions require flexibility in the design of the transition process, addressing the needs of the persons involved in an adaptive manner. Adaptivity is also considered crucial for the success of inclusive transitions. However, a systematic breakdown of the aspects that characterize the concept of adaptivity in the context of inclusive school entry is not available at this point. This article therefore provides a conceptualization of adaptivity in the inclusive transition to school as well as a review of the current literature focusing this topic. The goal is to develop a model that structures the various aspects of adaptivity at school entry and offers an overview of the way these aspects are important to design the transition successfully according to current findings of empirical research. Building on a concept of transitions informed by ecological systems theory, we are guided by the assumption that adaptivity at transition to school may occur in three forms: as a feature of the persons involved in the transition; as a feature of the processes that moderate the course of the transition; and as a feature of the structures that frame the transition. Based on this distinction, we develop a model that presents adaptivity in the inclusive transition to school.}, language = {en} } @article{SchmidtHolzgrabe2024, author = {Schmidt, Sebastian and Holzgrabe, Ulrike}, title = {Do the enantiomers of ketamine bind enantioselectively to human serum albumin?}, series = {European Journal of Pharmaceutical Sciences}, volume = {192}, journal = {European Journal of Pharmaceutical Sciences}, doi = {10.1016/j.ejps.2023.106640}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349791}, year = {2024}, abstract = {The binding of drugs to plasma proteins is an important process in the human body and has a significant influence on pharmacokinetic parameter. Human serum albumin (HSA) has the most important function as a transporter protein. The binding of ketamine to HSA has already been described in literature, but only of the racemate. The enantiomerically pure S-ketamine is used as injection solution for induction of anesthesia and has been approved by the Food and Drug Administration for the therapy of severe depression as a nasal spray in 2019. The question arises if there is enantioselective binding to HSA. Hence, the aim of this study was to investigate whether there is enantioselective binding of S-and R-ketamine to HSA or not. Ultrafiltration (UF) followed by chiral capillary electrophoretic analysis was used to determine the extent of protein binding. Bound fraction to HSA was 71.2 \% and 64.9 \% for enantiomerically pure R- and S-ketamine, respectively, and 66.5 \% for the racemate. Detailed binding properties were studied by Saturation Transfer Difference (STD)-, waterLOGSY- and Carr-Purcell-Meiboom-Gill (CPMG)-NMR spectroscopy. With all three methods, the aromatic ring and the N-methyl group could be identified as the structural moieties most strongly involved in binding of ketamine to HSA. pK\(_{aff}\) values determined using UF and NMR indicate that ketamine is a weak affinity ligand to HSA and no significant differences in binding behavior were found between the individual enantiomers and the racemate.}, language = {en} } @article{EberlRebsHoppeetal.2024, author = {Eberl, Hanna and Rebs, Sabine and Hoppe, Stefanie and Sedaghat-Hamedani, Farbod and Kayvanpour, Elham and Meder, Benjamin and Streckfuss-B{\"o}meke, Katrin}, title = {Generation of an RBM20-mutation-associated left-ventricular non-compaction cardiomyopathy iPSC line (UMGi255-A) into a DCM genetic background to investigate monogenetic cardiomyopathies}, series = {Stem Cell Research}, volume = {74}, journal = {Stem Cell Research}, issn = {1873-5061}, doi = {10.1016/j.scr.2023.103290}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350565}, year = {2024}, abstract = {RBM20 mutations account for 3 \% of genetic cardiomypathies and manifest with high penetrance and arrhythmogenic effects. Numerous mutations in the conserved RS domain have been described as causing dilated cardiomyopathy (DCM), whereas a particular mutation (p.R634L) drives development of a different cardiac phenotype: left-ventricular non-compaction cardiomyopathy. We generated a mutation-induced pluripotent stem cell (iPSC) line in which the RBM20-LVNC mutation p.R634L was introduced into a DCM patient line with rescued RBM20-p.R634W mutation. These DCM-634L-iPSC can be differentiated into functional cardiomyocytes to test whether this RBM20 mutation induces development of the LVNC phenotype within the genetic context of a DCM patient.}, language = {en} } @article{WillemsDettaBaldinietal.2024, author = {Willems, Suzanne and Detta, Elena and Baldini, Lorenzo and Tietz, Deniz and Trabocchi, Andrea and Brunschweiger, Andreas}, title = {Diversifying DNA-tagged amines by isocyanide multicomponent reactions for DNA-encoded library synthesis}, series = {ACS Omega}, volume = {9}, journal = {ACS Omega}, number = {7}, issn = {2470-1343}, doi = {10.1021/acsomega.3c07136}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349809}, pages = {7719-7724}, year = {2024}, abstract = {In DNA-encoded library synthesis, amine-substituted building blocks are prevalent. We explored isocyanide multicomponent reactions to diversify DNA-tagged amines and reported the Ugi-azide reaction with high yields and a good substrate scope. In addition, the Ugi-aza-Wittig reaction and the Ugi-4-center-3-component reaction, which used bifunctional carboxylic acids to provide lactams, were explored. Five-, six-, and seven-membered lactams were synthesized from solid support-coupled DNA-tagged amines and bifunctional building blocks, providing access to structurally diverse scaffolds.}, language = {en} } @article{JanzWalzCirnuetal.2024, author = {Janz, Anna and Walz, Katharina and Cirnu, Alexandra and Surjanto, Jessica and Urlaub, Daniela and Leskien, Miriam and Kohlhaas, Michael and Nickel, Alexander and Brand, Theresa and Nose, Naoko and W{\"o}rsd{\"o}rfer, Philipp and Wagner, Nicole and Higuchi, Takahiro and Maack, Christoph and Dudek, Jan and Lorenz, Kristina and Klopocki, Eva and Erg{\"u}n, S{\"u}leyman and Duff, Henry J. and Gerull, Brenda}, title = {Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes}, series = {Molecular Metabolism}, volume = {79}, journal = {Molecular Metabolism}, issn = {2212-8778}, doi = {10.1016/j.molmet.2023.101859}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350393}, year = {2024}, abstract = {Highlights • Loss of DNAJC19's DnaJ domain disrupts cardiac mitochondrial structure, leading to abnormal cristae formation in iPSC-CMs. • Impaired mitochondrial structures lead to an increased mitochondrial respiration, ROS and an elevated membrane potential. • Mutant iPSC-CMs show sarcomere dysfunction and a trend to more arrhythmias, resembling DCMA-associated cardiomyopathy. Background Dilated cardiomyopathy with ataxia (DCMA) is an autosomal recessive disorder arising from truncating mutations in DNAJC19, which encodes an inner mitochondrial membrane protein. Clinical features include an early onset, often life-threatening, cardiomyopathy associated with other metabolic features. Here, we aim to understand the metabolic and pathophysiological mechanisms of mutant DNAJC19 for the development of cardiomyopathy. Methods We generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two affected siblings with DCMA and a gene-edited truncation variant (tv) of DNAJC19 which all lack the conserved DnaJ interaction domain. The mutant iPSC-CMs and their respective control cells were subjected to various analyses, including assessments of morphology, metabolic function, and physiological consequences such as Ca\(^{2+}\) kinetics, contractility, and arrhythmic potential. Validation of respiration analysis was done in a gene-edited HeLa cell line (DNAJC19tv\(_{HeLa}\)). Results Structural analyses revealed mitochondrial fragmentation and abnormal cristae formation associated with an overall reduced mitochondrial protein expression in mutant iPSC-CMs. Morphological alterations were associated with higher oxygen consumption rates (OCRs) in all three mutant iPSC-CMs, indicating higher electron transport chain activity to meet cellular ATP demands. Additionally, increased extracellular acidification rates suggested an increase in overall metabolic flux, while radioactive tracer uptake studies revealed decreased fatty acid uptake and utilization of glucose. Mutant iPSC-CMs also showed increased reactive oxygen species (ROS) and an elevated mitochondrial membrane potential. Increased mitochondrial respiration with pyruvate and malate as substrates was observed in mutant DNAJC19tv HeLa cells in addition to an upregulation of respiratory chain complexes, while cellular ATP-levels remain the same. Moreover, mitochondrial alterations were associated with increased beating frequencies, elevated diastolic Ca\(^{2+}\) concentrations, reduced sarcomere shortening and an increased beat-to-beat rate variability in mutant cell lines in response to β-adrenergic stimulation. Conclusions Loss of the DnaJ domain disturbs cardiac mitochondrial structure with abnormal cristae formation and leads to mitochondrial dysfunction, suggesting that DNAJC19 plays an essential role in mitochondrial morphogenesis and biogenesis. Moreover, increased mitochondrial respiration, altered substrate utilization, increased ROS production and abnormal Ca\(^{2+}\) kinetics provide insights into the pathogenesis of DCMA-related cardiomyopathy.}, language = {en} } @article{HalfmannCastioniWetzeletal.2024, author = {Halfmann, Marie and Castioni, Noah and Wetzel, Lea and Koopmann, Anne and K{\"o}nig, Sarah and Schmieder, Astrid}, title = {Effects of the COVID-19 pandemic on the mental health of medical students and young physicians in Germany: Gender-specific results of an online survey}, series = {Heliyon}, volume = {10}, journal = {Heliyon}, number = {1}, issn = {2405-8440}, doi = {10.1016/j.heliyon.2023.e23727}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350502}, year = {2024}, abstract = {Background Healthcare workers and medical students faced new challenges during the COVID-19 pandemic. Processes within many hospitals were completely disrupted. In addition, the face to face teaching of medical students was drastically reduced. Those at risk of developing mental health problems appear to be younger health care workers and women. Objective To investigate potential COVID-19 pandemic-related gender differences in psychological distress among medical students and physicians in their first years of practice. Design and setting An anonymous survey was carried out online between December 1, 2021, and March 31, 2022, at the Mannheim Medical Faculty and the W{\"u}rzburg Medical Faculty, Germany, after obtaining informed consent. Primary outcome measures were changes in anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS), and changes in participants' current quality of life using the WHO Quality of Life BREF. Results The results show wave-like courses for perceived anxiety and burden overlapping with the course of the COVID-19 incidence. In comparison to men, women showed a significant higher increase in HADS (p = 0.005) and a reduced life quality (p = 0.007) after COVID-19. Both sexes showed different frequencies of the factors influencing quality of life, with the presence of a previous mental illness and mean anxiety having a significant higher negative impact in women. Conclusion Future and young female physicians reported a disproportionate higher burden during COVID-19 compared to their male colleges. These observations suggest an increased need for support and prevention efforts especially in this vulnerable population.}, language = {en} } @article{DuskeClausKroneetal.2024, author = {Duske, Helene and Claus, Heike and Krone, Manuel and L{\^a}m, Thi{\^e}n-Tr{\´i}}, title = {Prevalence of piperacillin/tazobactam resistance in invasive \(Haemophilus\) \(influenzae\) in Germany}, series = {JAC-Antimicrobial Resistance}, volume = {6}, journal = {JAC-Antimicrobial Resistance}, number = {1}, issn = {2632-1823}, doi = {10.1093/jacamr/dlad148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350424}, year = {2024}, abstract = {Background Haemophilus influenzae (Hi) is a Gram-negative bacterium that may cause sepsis or meningitis, treatment of which mainly includes β-lactam antibiotics. Since 2019 EUCAST breakpoints for piperacillin/tazobactam have been available. Little is known about the prevalence and mechanisms of piperacillin/tazobactam resistance in Hi. Objectives To provide reliable prevalence data for piperacillin/tazobactam resistance in Hi in Germany, to evaluate different antibiotic susceptibility testing methods and to examine possible resistance mechanisms. Methods According to EUCAST breakpoints, the MIC for piperacillin/tazobactam resistance is >0.25 mg/L. All invasive Hi in Germany from 2019 were examined by gradient agar diffusion (GAD) for piperacillin/tazobactam susceptibility. Piperacillin/tazobactam broth microdilution (BMD), piperacillin GAD on tazobactam-containing agar [piperacillin GAD on Mueller-Hinton agar with horse blood (MH-F)/tazobactam) and piperacillin/tazobactam agar dilution (AD) were used for confirmation. Phenotypic testing was complemented by ftsI sequencing. Results Piperacillin/tazobactam GAD resulted in 2.9\% (21/726) resistant Hi. BMD did not confirm piperacillin/tazobactam resistance. Two strains were found resistant by AD, of which one was also resistant using piperacillin GAD on MH-F/tazobactam. Overall, we found two strains with a piperacillin/tazobactam MIC >0.25 mg/L in at least two different tests (0.3\%). Both were β-lactamase-producing amoxicillin/clavulanate-resistant with PBP3 mutations characterized as group III-like+. Relevant PBP3 mutations occurred in six strains without phenotypic piperacillin/tazobactam resistance. These mutations suggest a reduced efficacy of β-lactam antibiotics in these isolates. Conclusions Piperacillin/tazobactam resistance prevalence in invasive Hi is low in Germany. Reduced susceptibility was correlated with PBP3 mutations, in particular with group III mutations.}, 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{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{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{HartmannsbergerScribaGuidolinetal.2024, author = {Hartmannsberger, Beate and Scriba, Sabrina and Guidolin, Carolina and Becker, Juliane and Mehling, Katharina and Doppler, Kathrin and Sommer, Claudia and Rittner, Heike L.}, title = {Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome}, series = {Journal of Neuroinflammation}, volume = {21}, journal = {Journal of Neuroinflammation}, doi = {10.1186/s12974-023-02969-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357164}, year = {2024}, abstract = {Background Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed. Methods We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells. Results Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin. Conclusions Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.}, language = {en} } @article{MittermeierSeidelScheineretal.2024, author = {Mittermeier, Sabrina and Seidel, Alexandra and Scheiner, Christin and Kleindienst, Nikolaus and Romanos, Marcel and Buerger, Arne}, title = {Emotional dysregulation and its pathways to suicidality in a community-based sample of adolescents}, series = {Child and Adolescent Psychiatry and Mental Health}, volume = {18}, journal = {Child and Adolescent Psychiatry and Mental Health}, issn = {1753-2000}, doi = {10.1186/s13034-023-00699-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357501}, year = {2024}, abstract = {Objective Effective suicide prevention for adolescents is urgently needed but difficult, as suicide models lack a focus on age-specific influencing factors such as emotional dysregulation. Moreover, examined predictors often do not specifically consider the contribution to the severity of suicidality. To determine which adolescents are at high risk of more severe suicidality, we examined the association between emotional dysregulation and severity of suicidality directly as well as indirectly via depressiveness and nonsuicidal self-injury. Method Adolescents from 18 high schools in Bavaria were included in this cross-sectional and questionnaire-based study as part of a larger prevention study. Data were collected between November 2021 and March 2022 and were analyzed from January 2023 to April 2023. Students in the 6th or 7th grade of high school (11-14 years) were eligible to participate. A total of 2350 adolescents were surveyed and data from 2117 students were used for the analyses after excluding incomplete data sets. Our main outcome variable was severity of suicidality (Paykel Suicide Scale, PSS). Additionally, we assessed emotional dysregulation (Difficulties in Emotion Regulation Scale, DERS-SF), depressiveness (Patient Health Questionnaire, PHQ-9) and nonsuicidal self-injury (Deliberate Self-Harm Inventory, DSHI). Results In total, 2117 adolescents (51.6\% female; mean age, 12.31 years [standard deviation: 0.67]) were included in the structural equation model (SEM). Due to a clear gender-specific influence, the model was calculated separately for male and female adolescents. For male adolescents, there was a significant indirect association between emotional dysregulation and severity of suicidality, mediated by depressiveness (β = 0.15, SE = .03, p = .008). For female adolescents, there was a significant direct path from emotional dysregulation to severity of suicidality and also indirect paths via depressiveness (β = 0.12, SE = .05, p = 0.02) and NSSI (β = 0.18, SE = .04, p < .001). Conclusions Our results suggest that gender-related risk markers in 11-14-year-olds need to be included in future suicide models to increase their predictive power. According to our findings, early detection and prevention interventions based on emotion regulation skills might be enhanced by including gender-specific adjustments for the co-occurrence of emotional dysregulation, depressiveness, and nonsuicidal self-injury in girls and the co-occurrence of emotional dysregulation and depressiveness in boys.}, language = {en} } @article{StanglPoppReisetal.2024, author = {Stangl, Stephanie and Popp, Maria and Reis, Stefanie and Sitter, Magdalena and Saal-Bauernschubert, Lena and Schießer, Selina and Kranke, Peter and Choorapoikayil, Suma and Weibel, Stephanie and Meybohm, Patrick}, title = {Reported outcomes in patients with iron deficiency or iron deficiency anemia undergoing major surgery: a systematic review of outcomes}, series = {Systematic Reviews}, volume = {13}, journal = {Systematic Reviews}, doi = {10.1186/s13643-023-02431-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357213}, year = {2024}, abstract = {Background Iron deficiency (ID) is the leading cause of anemia worldwide. The prevalence of preoperative ID ranges from 23 to 33\%. Preoperative anemia is associated with worse outcomes, making it important to diagnose and treat ID before elective surgery. Several studies indicated the effectiveness of intravenous iron supplementation in iron deficiency with or without anemia (ID(A)). However, it remains challenging to establish reliable evidence due to heterogeneity in utilized study outcomes. The development of a core outcome set (COS) can help to reduce this heterogeneity by proposing a minimal set of meaningful and standardized outcomes. The aim of our systematic review was to identify and assess outcomes reported in randomized controlled trials (RCTs) and observational studies investigating iron supplementation in iron-deficient patients with or without anemia. Methods We searched MEDLINE, CENTRAL, and ClinicalTrials.gov systematically from 2000 to April 1, 2022. RCTs and observational studies investigating iron supplementation in patients with a preoperative diagnosis of ID(A), were included. Study characteristics and reported outcomes were extracted. Outcomes were categorized according to an established outcome taxonomy. Quality of outcome reporting was assessed with a pre-specified tool. Reported clinically relevant differences for sample size calculation were extracted. Results Out of 2898 records, 346 underwent full-text screening and 13 studies (five RCTs, eight observational studies) with sufficient diagnostic inclusion criteria for iron deficiency with or without anemia (ID(A)) were eligible. It is noteworthy to mention that 49 studies were excluded due to no confirmed diagnosis of ID(A). Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92\%) reported outcomes within the 'blood and lymphatic system' domain, followed by "adverse event" (77\%) and "need for further resources" (77\%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33\%) of six prospective studies were registered prospectively of which one (17\%) showed no signs of selective outcome reporting. Conclusion This systematic review comprehensively depicts the heterogeneity of reported outcomes in studies investigating iron supplementation in ID(A) patients regarding exact definitions and timing. Our analysis provides a systematic base for consenting to a minimal COS. Systematic review registration PROSPERO CRD42020214247}, language = {en} } @article{MeinertJessenHufnageletal.2024, author = {Meinert, Madlen and Jessen, Christina and Hufnagel, Anita and Kreß, Julia Katharina Charlotte and Burnworth, Mychal and D{\"a}ubler, Theo and Gallasch, Till and Da Xavier Silva, Thamara Nishida and Dos Santos, Anc{\´e}ly Ferreira and Ade, Carsten Patrick and Schmitz, Werner and Kneitz, Susanne and Friedmann Angeli, Jos{\´e} Pedro and Meierjohann, Svenja}, title = {Thiol starvation triggers melanoma state switching in an ATF4 and NRF2-dependent manner}, series = {Redox Biology}, volume = {70}, journal = {Redox Biology}, doi = {10.1016/j.redox.2023.103011}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350328}, year = {2024}, abstract = {The cystine/glutamate antiporter xCT is an important source of cysteine for cancer cells. Once taken up, cystine is reduced to cysteine and serves as a building block for the synthesis of glutathione, which efficiently protects cells from oxidative damage and prevents ferroptosis. As melanomas are particularly exposed to several sources of oxidative stress, we investigated the biological role of cysteine and glutathione supply by xCT in melanoma. xCT activity was abolished by genetic depletion in the Tyr::CreER; Braf\(^{CA}\); Pten\(^{lox/+}\) melanoma model and by acute cystine withdrawal in melanoma cell lines. Both interventions profoundly impacted melanoma glutathione levels, but they were surprisingly well tolerated by murine melanomas in vivo and by most human melanoma cell lines in vitro. RNA sequencing of human melanoma cells revealed a strong adaptive upregulation of NRF2 and ATF4 pathways, which orchestrated the compensatory upregulation of genes involved in antioxidant defence and de novo cysteine biosynthesis. In addition, the joint activation of ATF4 and NRF2 triggered a phenotypic switch characterized by a reduction of differentiation genes and induction of pro-invasive features, which was also observed after erastin treatment or the inhibition of glutathione synthesis. NRF2 alone was capable of inducing the phenotypic switch in a transient manner. Together, our data show that cystine or glutathione levels regulate the phenotypic plasticity of melanoma cells by elevating ATF4 and NRF2.}, language = {en} } @article{NollWuerthner2024, author = {Noll, Niklas and W{\"u}rthner, Frank}, title = {Bioinspired water preorganization in confined space for efficient water oxidation catalysis in metallosupramolecular ruthenium architectures}, series = {Accounts of Chemical Research}, volume = {57}, journal = {Accounts of Chemical Research}, number = {10}, issn = {0001-4842}, doi = {10.1021/acs.accounts.4c00148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361232}, pages = {1538-1549}, year = {2024}, abstract = {Conspectus Nature has established a sustainable way to maintain aerobic life on earth by inventing one of the most sophisticated biological processes, namely, natural photosynthesis, which delivers us with organic matter and molecular oxygen derived from the two abundant resources sunlight and water. The thermodynamically demanding photosynthetic water splitting is catalyzed by the oxygen-evolving complex in photosystem II (OEC-PSII), which comprises a distorted tetramanganese-calcium cluster (CaMn\(_4\)O\(_5\)) as catalytic core. As an ubiquitous concept for fine-tuning and regulating the reactivity of the active site of metalloenzymes, the surrounding protein domain creates a sophisticated environment that promotes substrate preorganization through secondary, noncovalent interactions such as hydrogen bonding or electrostatic interactions. Based on the high-resolution X-ray structure of PSII, several water channels were identified near the active site, which are filled with extensive hydrogen-bonding networks of preorganized water molecules, connecting the OEC with the protein surface. As an integral part of the outer coordination sphere of natural metalloenzymes, these channels control the substrate and product delivery, carefully regulate the proton flow by promoting pivotal proton-coupled electron transfer processes, and simultaneously stabilize short-lived oxidized intermediates, thus highlighting the importance of an ordered water network for the remarkable efficiency of the natural OEC. Transferring this concept from nature to the engineering of artificial metal catalysts for fuel production has fostered the fascinating field of metallosupramolecular chemistry by generating defined cavities that conceptually mimic enzymatic pockets. However, the application of supramolecular approaches to generate artificial water oxidation catalysts remained scarce prior to our initial reports, since such molecular design strategies for efficient activation of substrate water molecules in confined nanoenvironments were lacking. In this Account, we describe our research efforts on combining the state-of-the art Ru(bda) catalytic framework with structurally programmed ditopic ligands to guide the water oxidation process in defined metallosupramolecular assemblies in spatial proximity. We will elucidate the governing factors that control the quality of hydrogen-bonding water networks in multinuclear cavities of varying sizes and geometries to obtain high-performance, state-of-the-art water oxidation catalysts. Pushing the boundaries of artificial catalyst design, embedding a single catalytic Ru center into a well-defined molecular pocket enabled sophisticated water preorganization in front of the active site through an encoded basic recognition site, resulting in high catalytic rates comparable to those of the natural counterpart OEC-PSII. To fully explore their potential for solar fuel devices, the suitability of our metallosupramolecular assemblies was demonstrated under (electro)chemical and photocatalytic water oxidation conditions. In addition, testing the limits of structural diversity allowed the fabrication of self-assembled linear coordination oligomers as novel photocatalytic materials and long-range ordered covalent organic framework (COF) materials as recyclable and long-term stable solid-state materials for future applications.}, language = {en} } @article{KirchnerSchrammIvanovaetal.2024, author = {Kirchner, Philipp H. and Schramm, Louis and Ivanova, Svetlana and Shoyama, Kazutaka and W{\"u}rthner, Frank and Beuerle, Florian}, title = {A water-stable boronate ester cage}, series = {Journal of the American Chemical Society}, volume = {146}, journal = {Journal of the American Chemical Society}, number = {8}, issn = {0002-7863}, doi = {10.1021/jacs.3c12002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361245}, pages = {5305-5315}, year = {2024}, abstract = {The reversible condensation of catechols and boronic acids to boronate esters is a paradigm reaction in dynamic covalent chemistry. However, facile backward hydrolysis is detrimental for stability and has so far prevented applications for boronate-based materials. Here, we introduce cubic boronate ester cages 6 derived from hexahydroxy tribenzotriquinacenes and phenylene diboronic acids with ortho-t-butyl substituents. Due to steric shielding, dynamic exchange at the Lewis acidic boron sites is feasible only under acid or base catalysis but fully prevented at neutral conditions. For the first time, boronate ester cages 6 tolerate substantial amounts of water or alcohols both in solution and solid state. The unprecedented applicability of these materials under ambient and aqueous conditions is showcased by efficient encapsulation and on-demand release of β-carotene dyes and heterogeneous water oxidation catalysis after the encapsulation of ruthenium catalysts.}, language = {en} } @article{GutzeitWellerMuthetal.2024, author = {Gutzeit, Julian and Weller, Lisa and Muth, Felicitas and K{\"u}rten, Jens and Huestegge, Lynn}, title = {Eye did this! Sense of agency in eye movements}, series = {Acta Psychologica}, volume = {243}, journal = {Acta Psychologica}, doi = {10.1016/j.actpsy.2023.104121}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349819}, year = {2024}, abstract = {This study investigates the sense of agency (SoA) for saccades with implicit and explicit agency measures. In two eye tracking experiments, participants moved their eyes towards on-screen stimuli that subsequently changed color. Participants then either reproduced the temporal interval between saccade and color-change (Experiment 1) or reported the time points of these events with an auditory Libet clock (Experiment 2) to measure temporal binding effects as implicit indices of SoA. Participants were either made to believe to exert control over the color change or not (agency manipulation). Explicit ratings indicated that the manipulation of causal beliefs and hence agency was successful. However, temporal binding was only evident for caused effects, and only when a sufficiently sensitive procedure was used (auditory Libet clock). This suggests a feebler connection between temporal binding and SoA than previously proposed. The results also provide evidence for a relatively fast acquisition of sense of agency for previously never experienced types of action-effect associations. This indicates that the underlying processes of action control may be rooted in more intricate and adaptable cognitive models than previously thought. Oculomotor SoA as addressed in the present study presumably represents an important cognitive foundation of gaze-based social interaction (social sense of agency) or gaze-based human-machine interaction scenarios. Public significance statement: In this study, sense of agency for eye movements in the non-social domain is investigated in detail, using both explicit and implicit measures. Therefore, it offers novel and specific insights into comprehending sense of agency concerning effects induced by eye movements, as well as broader insights into agency pertaining to entirely newly acquired types of action-effect associations. Oculomotor sense of agency presumably represents an important cognitive foundation of gaze-based social interaction (social agency) or gaze-based human-machine interaction scenarios. Due to peculiarities of the oculomotor domain such as the varying degree of volitional control, eye movements could provide new information regarding more general theories of sense of agency in future research.}, language = {en} } @article{SteinhardtCejkaChenetal.2024, author = {Steinhardt, Maximilian J. and Cejka, Vladimir and Chen, Mengmeng and B{\"a}uerlein, Sabrina and Sch{\"a}fer, Julia and Adrah, Ali and Ihne-Schubert, Sandra M. and Papagianni, Aikaterini and Kort{\"u}m, K. Martin and Morbach, Caroline and St{\"o}rk, Stefan}, title = {Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study}, series = {Journal of Clinical Medicine}, volume = {13}, journal = {Journal of Clinical Medicine}, number = {1}, issn = {2077-0383}, doi = {10.3390/jcm13010283}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-356024}, year = {2024}, abstract = {Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1\% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5\% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.}, language = {en} } @article{SchneiderSeebauerBeuerleetal.2024, author = {Schneider, Tilman and Seebauer, Florian and Beuerle, Florian and W{\"u}rthner, Frank}, title = {A monodisperse, end-capped Ru(bda) oligomer with outstanding performance in heterogeneous electrochemical water oxidation}, series = {Advanced Materials Technologies}, volume = {9}, journal = {Advanced Materials Technologies}, number = {11}, issn = {2365-709X}, doi = {10.1002/admt.202301721}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363133}, year = {2024}, abstract = {AbstractWater oxidation catalysis is a key step for sustainable fuel production by water splitting into hydrogen and oxygen. The synthesis of a novel coordination oligomer based on four Ru(bda) (bda = 2,2′-bipyridine-6,6′-dicarboxylate) centers, three 4,4′-bipyridine (4,4′-bpy) linkers, and two 4-picoline (4-pic) end caps is reported. The monodispersity of this tetranuclear compound is characterized by NMR techniques. Heterogeneous electrochemical water oxidation after immobilization on multi-walled carbon nanotubes (MWCNTs) shows catalytic performance unprecedented for this compound class, with a turnover frequency (TOF) of 133 s\(^{-1}\) and a turnover number (TON) of 4.89 × 10\(^6\), at a current density of 43.8 mA cm\(^{-2}\) and a potential of 1.45 V versus normal hydrogen electrode (NHE).}, language = {en} } @article{LandmannBreilHuesteggeetal.2024, author = {Landmann, Eva and Breil, Christina and Huestegge, Lynn and B{\"o}ckler, Anne}, title = {The semantics of gaze in person perception: a novel qualitative-quantitative approach}, series = {Scientific Reports}, volume = {14}, journal = {Scientific Reports}, number = {1}, issn = {2045-2322}, doi = {10.1038/s41598-024-51331-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361413}, year = {2024}, abstract = {Interpreting gaze behavior is essential in evaluating interaction partners, yet the 'semantics of gaze' in dynamic interactions are still poorly understood. We aimed to comprehensively investigate effects of gaze behavior patterns in different conversation contexts, using a two-step, qualitative-quantitative procedure. Participants watched video clips of single persons listening to autobiographic narrations by another (invisible) person. The listener's gaze behavior was manipulated in terms of gaze direction, frequency and direction of gaze shifts, and blink frequency; emotional context was manipulated through the valence of the narration (neutral/negative). In Experiment 1 (qualitative-exploratory), participants freely described which states and traits they attributed to the listener in each condition, allowing us to identify relevant aspects of person perception and to construct distinct rating scales that were implemented in Experiment 2 (quantitative-confirmatory). Results revealed systematic and differential meanings ascribed to the listener's gaze behavior. For example, rapid blinking and fast gaze shifts were rated more negatively (e.g., restless and unnatural) than slower gaze behavior; downward gaze was evaluated more favorably (e.g., empathetic) than other gaze aversion types, especially in the emotionally negative context. Overall, our study contributes to a more systematic understanding of flexible gaze semantics in social interaction.}, language = {en} } @article{ScheinerDaunkeSeideletal.2023, author = {Scheiner, Christin and Daunke, Andrea and Seidel, Alexandra and Mittermeier, Sabrina and Romanos, Marcel and K{\"o}lch, Michael and Buerger, Arne}, title = {LessStress - how to reduce stress in school: evaluation of a universal stress prevention in schools: study protocol of a cluster-randomised controlled trial}, series = {Trials}, volume = {24}, journal = {Trials}, number = {1}, doi = {10.1186/s13063-022-06970-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300393}, year = {2023}, abstract = {Background Chronic stress is detrimental to health, and children and young people have had to cope with significantly more stress since the start of the COVID-19 pandemic. In particular, stress at school and in relation to learning is a major problem in this age group. Studies in Germany have indicated that the pandemic has led to a reduced quality of life (QoL) and an increased risk for psychiatric disorders in children and adolescents. Schools are an ideal setting for interventions against stress, which is one of the strongest predictors for the development of psychosocial problems. The present study seeks to address stress by means of a short prevention training programme in schools, including emotion regulation, mindfulness, and self-compassion. In addition to information material for self-study, students should have the opportunity to actively deal with the topic of stress and develop coping strategies within a short space of time. In contrast to very long stress reduction programmes that often last several weeks, the programme is delivered in just 90 min. Methods The effectiveness of the short and economical prevention programme LessStress will be examined in a cluster-randomised controlled trial (RCT) encompassing 1894 students. At several measurement time points, students from two groups (intervention and control) will be asked about their subjectively perceived stress levels, among other aspects. Due to the clustered nature of the data, mainly multilevel analyses will be performed. Discussion In Germany, there are no nationwide universal prevention programmes for students against stress in schools, and this gap has become more evident since the outbreak of the pandemic. Universal stress prevention in schools may be a starting point to promote resilience. By dealing with stress in a healthy way, mental health can be strengthened and maintained. Moreover, to reach at-risk students at an early stage, we advocate for a stronger networking between child psychiatry and schools.}, language = {en} } @article{Klug2023, author = {Klug, Florian}, title = {The Theologian's Socratic Role in today's Scientific World}, series = {Doctrine \& Life}, volume = {73}, journal = {Doctrine \& Life}, number = {2}, issn = {0012-4664}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303554}, pages = {35-45}, year = {2023}, abstract = {In the scientific search for truth, the correspondence theory is predominant to decipher what counts as true. In this approach, scientific knowledge becomes empirically demonstrable and thus enclosed to the sphere of immanence. However, in theology's approach to question the given status of being human and the world's development as creation, theology does not adhere to answers that are contained within the sphere of demonstrable knowledge or mundanity, and thereby theology presents a fundamentally different conception of truth, Jesus Christ the living truth. In opposition to drawing on empirical proof, I want to reread Christian theology in a Socratic manner that employs irony to question overly simple methodologies and seek further insights what it means to be human and be engaged in the scientific search for truth if the authority of knowledge does not lie within humanity's grasp. In doing so, theology's role is an annoying, yet necessary irritation within the field of today's academia.}, language = {en} } @article{KressEgenolfSommeretal.2023, author = {Kreß, Luisa and Egenolf, Nadine and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan}, title = {Cytokine expression profiles in white blood cells of patients with small fiber neuropathy}, series = {BMC Neuroscience}, volume = {24}, journal = {BMC Neuroscience}, number = {1}, doi = {10.1186/s12868-022-00770-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300619}, year = {2023}, abstract = {Background The role of cytokines in the pathophysiology, diagnosis, and prognosis of small fiber neuropathy (SFN) is incompletely understood. We studied expression profiles of selected pro- and anti-inflammatory cytokines in RNA from white blood cells (WBC) of patients with a medical history and a clinical phenotype suggestive for SFN and compared data with healthy controls. Methods We prospectively recruited 52 patients and 21 age- and sex-matched healthy controls. Study participants were characterized in detail and underwent complete neurological examination. Venous blood was drawn for routine and extended laboratory tests, and for WBC isolation. Systemic RNA expression profiles of the pro-inflammatory cytokines interleukin (IL)-1ß, IL-2, IL-8, tumor necrosis factor-alpha (TNF) and the anti-inflammatory cytokines IL-4, IL-10, transforming growth factor beta-1 (TGF) were analyzed. Protein levels of IL-2, IL-8, and TNF were measured in serum of patients and controls. Receiver operating characteristic (ROC)-curve analysis was used to determine the accuracy of IL-2, IL-8, and TNF in differentiating patients and controls. To compare the potential discriminatory efficacy of single versus combined cytokines, equality of different AUCs was tested. Results WBC gene expression of IL-2, IL-8, and TNF was higher in patients compared to healthy controls (IL-2: p = 0.02; IL-8: p = 0.009; TNF: p = 0.03) and discriminated between the groups (area under the curve (AUC) ≥ 0.68 for each cytokine) with highest diagnostic accuracy reached by combining the three cytokines (AUC = 0.81, sensitivity = 70\%, specificity = 86\%). Subgroup analysis revealed the following differences: IL-8 and TNF gene expression levels were higher in female patients compared to female controls (IL-8: p = 0.01; TNF: p = 0.03). The combination of TNF with IL-2 and TNF with IL-2 and IL-8 discriminated best between the study groups. IL-2 was higher expressed in patients with moderate pain compared to those with severe pain (p = 0.02). Patients with acral pain showed higher IL-10 gene expression compared to patients with generalized pain (p = 0.004). We further found a negative correlation between the relative gene expression of IL-2 and current pain intensity (p = 0.02). Serum protein levels of IL-2, IL-8, and TNF did not differ between patients and controls. Conclusions We identified higher systemic gene expression of IL-2, IL-8, and TNF in SFN patients than in controls, which may be of potential relevance for diagnostics and patient stratification.}, language = {en} } @article{DresenLeeHilletal.2023, author = {Dresen, Ellen and Lee, Zheng-Yii and Hill, Aileen and Notz, Quirin and Patel, Jayshil J. and Stoppe, Christian}, title = {History of scurvy and use of vitamin C in critical illness: A narrative review}, series = {Nutrition in Clinical Practice}, volume = {38}, journal = {Nutrition in Clinical Practice}, number = {1}, doi = {10.1002/ncp.10914}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318176}, pages = {46 -- 54}, year = {2023}, abstract = {In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness—a condition also resulting in death of thousands in the 21st century—has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019.}, language = {en} } @article{RackeveiKarnkowskaWolf2023, author = {Rackevei, Antonia S. and Karnkowska, Anna and Wolf, Matthias}, title = {18S rDNA sequence-structure phylogeny of the Euglenophyceae (Euglenozoa, Euglenida)}, series = {Journal of Eukaryotic Microbiology}, volume = {70}, journal = {Journal of Eukaryotic Microbiology}, number = {2}, doi = {10.1111/jeu.12959}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311896}, year = {2023}, abstract = {The phylogeny of Euglenophyceae (Euglenozoa, Euglenida) has been discussed for decades with new genera being described in the last few years. In this study, we reconstruct a phylogeny using 18S rDNA sequence and structural data simultaneously. Using homology modeling, individual secondary structures were predicted. Sequence-structure data are encoded and automatically aligned. Here, we present a sequence-structure neighbor-joining tree of more than 300 taxa classified as Euglenophyceae. Profile neighbor-joining was used to resolve the basal branching pattern. Neighbor-joining, maximum parsimony, and maximum likelihood analyses were performed using sequence-structure information for manually chosen subsets. All analyses supported the monophyly of Eutreptiella, Discoplastis, Lepocinclis, Strombomonas, Cryptoglena, Monomorphina, Euglenaria, and Colacium. Well-supported topologies were generally consistent with previous studies using a combined dataset of genetic markers. Our study supports the simultaneous use of sequence and structural data to reconstruct more accurate and robust trees. The average bootstrap value is significantly higher than the average bootstrap value obtained from sequence-only analyses, which is promising for resolving relationships between more closely related taxa.}, language = {en} } @article{KernerKraussMaihoffetal.2023, author = {Kerner, Janika M. and Krauss, Jochen and Maihoff, Fabienne and Bofinger, Lukas and Classen, Alice}, title = {Alpine butterflies want to fly high: Species and communities shift upwards faster than their host plants}, series = {Ecology}, volume = {104}, journal = {Ecology}, number = {1}, doi = {10.1002/ecy.3848}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312015}, year = {2023}, abstract = {Despite sometimes strong codependencies of insect herbivores and plants, the responses of individual taxa to accelerating climate change are typically studied in isolation. For this reason, biotic interactions that potentially limit species in tracking their preferred climatic niches are ignored. Here, we chose butterflies as a prominent representative of herbivorous insects to investigate the impacts of temperature changes and their larval host plant distributions along a 1.4-km elevational gradient in the German Alps. Following a sampling protocol of 2009, we revisited 33 grassland plots in 2019 over an entire growing season. We quantified changes in butterfly abundance and richness by repeated transect walks on each plot and disentangled the direct and indirect effects of locally assessed temperature, site management, and larval and adult food resource availability on these patterns. Additionally, we determined elevational range shifts of butterflies and host plants at both the community and species level. Comparing the two sampled years (2009 and 2019), we found a severe decline in butterfly abundance and a clear upward shift of butterflies along the elevational gradient. We detected shifts in the peak of species richness, community composition, and at the species level, whereby mountainous species shifted particularly strongly. In contrast, host plants showed barely any change, neither in connection with species richness nor individual species shifts. Further, temperature and host plant richness were the main drivers of butterfly richness, with change in temperature best explaining the change in richness over time. We concluded that host plants were not yet hindering butterfly species and communities from shifting upwards. However, the mismatch between butterfly and host plant shifts might become a problem for this very close plant-herbivore relationship, especially toward higher elevations, if butterflies fail to adapt to new host plants. Further, our results support the value of conserving traditional extensive pasture use as a promoter of host plant and, hence, butterfly richness.}, language = {en} } @article{FrickeRedlichZhangetal.2023, author = {Fricke, Ute and Redlich, Sarah and Zhang, Jie and Benjamin, Caryl S. and Englmeier, Jana and Ganuza, Cristina and Haensel, Maria and Riebl, Rebekka and Rojas-Botero, Sandra and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Steffan-Dewenter, Ingolf}, title = {Earlier flowering of winter oilseed rape compensates for higher pest pressure in warmer climates}, series = {Journal of Applied Ecology}, volume = {60}, journal = {Journal of Applied Ecology}, number = {2}, doi = {10.1111/1365-2664.14335}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312562}, pages = {365 -- 375}, year = {2023}, abstract = {Global warming can increase insect pest pressure by enhancing reproductive rates. Whether this translates into yield losses depends on phenological synchronisation of pests with their host plants and natural enemies. Simultaneously, landscape composition may mitigate climate effects by shaping the resource availability for pests and their antagonists. Here, we study the combined effects of temperature and landscape composition on pest abundances, larval parasitism, crop damage and yield, while also considering crop phenology, to identify strategies for sustainable management of oilseed rape (OSR) pests under warming climates. In all, 29 winter OSR crop fields were investigated in different climates (defined by multi-annual mean temperature, MAT) and landscape contexts in Bavaria, Germany. We measured abundances of adult pollen beetles and stem weevil larvae, pollen beetle larval parasitism, bud loss, stem damage and seed yield, and calculated the flowering date from growth stage observations. Landscape parameters (proportion of non-crop and OSR area, change in OSR area relative to the previous year) were calculated at six spatial scales (0.6-5 km). Pollen beetle abundance increased with MAT but to different degrees depending on the landscape context, that is, increased less strongly when OSR proportions were high (1-km scale), interannually constant (5-km scale) or both. In contrast, stem weevil abundance and stem damage did not respond to landscape composition nor MAT. Pollen beetle larval parasitism was overall low, but occasionally exceeded 30\% under both low and high MAT and with reduced OSR area (0.6-km scale). Despite high pollen beetle abundance in warm climates, yields were high when OSR flowered early. Thereby, higher temperatures favoured early flowering. Only among late-flowering OSR crop fields yield was higher in cooler than warmer climates. Bud loss responded analogously. Landscape composition did not substantially affect bud loss and yield. Synthesis and applications: Earlier flowering of winter OSR compensates for higher pollen beetle abundance in warmer climates, while interannual continuity of OSR area prevents high pollen beetle abundance in the first place. Thus, regional coordination of crop rotation and crop management promoting early flowering may contribute to sustainable pest management in OSR under current and future climatic conditions.}, language = {en} } @article{HutmacherSchlaegerMeerson2023, author = {Hutmacher, Fabian and Schl{\"a}ger, Linus and Meerson, Rinat}, title = {Autobiographical memory in the digital age: Insights based on the subjective reports of users of smart journaling apps}, series = {Applied Cognitive Psychology}, volume = {37}, journal = {Applied Cognitive Psychology}, number = {4}, issn = {0888-4080}, doi = {10.1002/acp.4033}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318620}, pages = {686 -- 698}, year = {2023}, abstract = {Humans have long used external memory aids to support remembering. However, modern digital technologies could facilitate recording and remembering personal information in an unprecedented manner. The present research sought to understand the potential impact of these technologies on autobiographical memory based on interviews with users of smart journaling apps. In Study 1 (N = 12), participants who had no prior experience with smart journaling apps tested the app Day One for 2 weeks and were interviewed about their subjective perceptions afterwards. In order to cross-validate the obtained findings, Study 2 (N = 4) was based on in-depth interviews with long-time users of different smart journaling apps. Taken together, the two studies provide insights into the way autobiographical remembering may change in the digital age - but also into the opportunities and risks potentially associated with the use of technologies that allow creating a detailed and multimedia-based record of one's life.}, language = {en} } @article{KrieterRuethLemkeetal.2023, author = {Krieter, Detlef H. and R{\"u}th, Marieke and Lemke, Horst-Dieter and Wanner, Christoph}, title = {Clinical performance comparison of two medium cut-off dialyzers}, series = {Therapeutic Apheresis and Dialysis}, volume = {27}, journal = {Therapeutic Apheresis and Dialysis}, number = {2}, doi = {10.1111/1744-9987.13919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318643}, pages = {284 -- 292}, year = {2023}, abstract = {Introduction Medium-cut-off (MCO) dialyzers may beneficially impact outcomes in patients on hemodialysis. Methods In a randomized, controlled trial in maintenance hemodialysis patients, the new Nipro ELISIO-17HX MCO dialyzer was compared to the Baxter Theranova 400 filter regarding middle molecule removal. Furthermore, the suitability of two assays for free lambda-light chain (λFLC) detection (Freelite vs. N-Latex) was verified. Results ELISIO-HX achieved slightly lower reduction ratios for β2-microglobulin (71.8 ± 6.0 vs. 75.3 ± 5.8\%; p = 0.001), myoglobin (54.7 ± 8.6 vs. 64.9 ± 8.7\%; p < 0.001), and kappa-FLC (62.1 ± 8.8 vs. 56.3 ± 7.7\%; p = 0.021). λFLC reduction ratios were more conclusive with the Freelite assay and not different between ELISIO-HX and Theranova (28.4 ± 3.9 vs. 38.7 ± 13.4\%; p = 0.069). The albumin loss of Theranova was considerably higher (2.14 ± 0.45 vs. 0.77 ± 0.25 g; p = 0.001) and the Global Removal ScoreLoss alb largely inferior (30.6 ± 7.4 vs. 82.4 ± 29.2\%/g; p = 0.006) to ELISIO-HX. Conclusions The new ELISIO-HX expands the choice of dialyzers for MCO hemodialysis.}, language = {en} } @article{GrausLiRathjeetal.2023, author = {Graus, Dorothea and Li, Kunkun and Rathje, Jan M. and Ding, Meiqi and Krischke, Markus and M{\"u}ller, Martin J. and Cuin, Tracey Ann and Al-Rasheid, Khaled A. S. and Scherzer, S{\"o}nke and Marten, Irene and Konrad, Kai R. and Hedrich, Rainer}, title = {Tobacco leaf tissue rapidly detoxifies direct salt loads without activation of calcium and SOS signaling}, series = {New Phytologist}, volume = {237}, journal = {New Phytologist}, number = {1}, doi = {10.1111/nph.18501}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312152}, pages = {217 -- 231}, year = {2023}, abstract = {Salt stress is a major abiotic stress, responsible for declining agricultural productivity. Roots are regarded as hubs for salt detoxification, however, leaf salt concentrations may exceed those of roots. How mature leaves manage acute sodium chloride (NaCl) stress is mostly unknown. To analyze the mechanisms for NaCl redistribution in leaves, salt was infiltrated into intact tobacco leaves. It initiated pronounced osmotically-driven leaf movements. Leaf downward movement caused by hydro-passive turgor loss reached a maximum within 2 h. Salt-driven cellular water release was accompanied by a transient change in membrane depolarization but not an increase in cytosolic calcium ion (Ca\(^{2+}\)) level. Nonetheless, only half an hour later, the leaves had completely regained turgor. This recovery phase was characterized by an increase in mesophyll cell plasma membrane hydrogen ion (H\(^{+}\)) pumping, a salt uptake-dependent cytosolic alkalization, and a return of the apoplast osmolality to pre-stress levels. Although, transcript numbers of abscisic acid- and Salt Overly Sensitive pathway elements remained unchanged, salt adaptation depended on the vacuolar H\(^{+}\)/Na\(^{+}\)-exchanger NHX1. Altogether, tobacco leaves can detoxify sodium ions (Na\(^{+}\)) rapidly even under massive salt loads, based on pre-established posttranslational settings and NHX1 cation/H+ antiport activity. Unlike roots, signaling and processing of salt stress in tobacco leaves does not depend on Ca\(^{2+}\) signaling.}, language = {en} } @article{DieboldSchoenemannEilersetal.2023, author = {Diebold, Mathias and Sch{\"o}nemann, Lars and Eilers, Martin and Sotriffer, Christoph and Schindelin, Hermann}, title = {Crystal structure of a covalently linked Aurora-A-MYCN complex}, series = {Acta Crystallographica}, volume = {D79}, journal = {Acta Crystallographica}, doi = {10.1107/s2059798322011433}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318855}, pages = {1 -- 9}, year = {2023}, abstract = {Formation of the Aurora-A-MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A-MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A-MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.}, language = {en} } @article{DawoodBreuerStebanietal.2023, author = {Dawood, Peter and Breuer, Felix and Stebani, Jannik and Burd, Paul and Homolya, Istv{\´a}n and Oberberger, Johannes and Jakob, Peter M. and Blaimer, Martin}, title = {Iterative training of robust k-space interpolation networks for improved image reconstruction with limited scan specific training samples}, series = {Magnetic Resonance in Medicine}, volume = {89}, journal = {Magnetic Resonance in Medicine}, number = {2}, doi = {10.1002/mrm.29482}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312306}, pages = {812 -- 827}, year = {2023}, abstract = {To evaluate an iterative learning approach for enhanced performance of robust artificial-neural-networks for k-space interpolation (RAKI), when only a limited amount of training data (auto-calibration signals [ACS]) are available for accelerated standard 2D imaging. Methods In a first step, the RAKI model was tailored for the case of limited training data amount. In the iterative learning approach (termed iterative RAKI [iRAKI]), the tailored RAKI model is initially trained using original and augmented ACS obtained from a linear parallel imaging reconstruction. Subsequently, the RAKI convolution filters are refined iteratively using original and augmented ACS extracted from the previous RAKI reconstruction. Evaluation was carried out on 200 retrospectively undersampled in vivo datasets from the fastMRI neuro database with different contrast settings. Results For limited training data (18 and 22 ACS lines for R = 4 and R = 5, respectively), iRAKI outperforms standard RAKI by reducing residual artifacts and yields better noise suppression when compared to standard parallel imaging, underlined by quantitative reconstruction quality metrics. Additionally, iRAKI shows better performance than both GRAPPA and standard RAKI in case of pre-scan calibration with varying contrast between training- and undersampled data. Conclusion RAKI benefits from the iterative learning approach, which preserves the noise suppression feature, but requires less original training data for the accurate reconstruction of standard 2D images thereby improving net acceleration.}, language = {en} } @article{PhilippBertermannRadius2023, author = {Philipp, Michael S. M. and Bertermann, R{\"u}diger and Radius, Udo}, title = {Activation of Ge-H and Sn-H Bonds with N-Heterocyclic Carbenes and a Cyclic (Alkyl)(amino)carbene}, series = {Chemistry - A European Journal}, volume = {29}, journal = {Chemistry - A European Journal}, number = {3}, doi = {10.1002/chem.202202493}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311929}, year = {2023}, abstract = {A study of the reactivity of several N-heterocyclic carbenes (NHCs) and the cyclic (alkyl)(amino)carbene 1-(2,6-di-iso-propylphenyl)-3,3,5,5-tetramethyl-pyrrolidin-2-ylidene (cAAC\(^{Me}\)) with the group 14 hydrides GeH2Mes2 and SnH2Me2 (Me=CH\(_{3}\), Mes=1,3,5-(CH\(_{3}\))\(_{3}\)C\(_{6}\)H\(_{2}\)) is presented. The reaction of GeH\(_{2}\)Mes\(_{2}\) with cAAC\(^{Me}\) led to the insertion of cAAC\(^{Me}\) into one Ge-H bond to give cAAC\(^{Me}\)H-GeHMes\(_{2}\) (1). If 1,3,4,5-tetramethyl-imidazolin-2-ylidene (Me\(_{2}\)Im\(^{Me}\)) was used as the carbene, NHC-mediated dehydrogenative coupling occurred, which led to the NHC-stabilized germylene Me\(_{2}\)Im\(^{Me}\)⋅GeMes\(_{2}\) (2). The reaction of SnH\(_{2}\)Me\(_{2}\) with cAAC\(^{Me}\) also afforded the insertion product cAAC\(^{Me}\)H-SnHMe\(_{2}\) (3), and reaction of two equivalents Me\(_{2}\)Im\(^{Me}\) with SnH\(_{2}\)Me\(_{2}\) gave the NHC-stabilized stannylene Me\(_{2}\)Im\(^{Me}\)⋅SnMe\(_{2}\) (4). If the sterically more demanding NHCs Me\(_{2}\)Im\(^{Me}\), 1,3-di-isopropyl-4,5-dimethyl-imidazolin-2-ylidene (iPr\(_{2}\)Im\(^{Me}\)) and 1,3-bis-(2,6-di-isopropylphenyl)-imidazolin-2-ylidene (Dipp\(_{2}\)Im) were employed, selective formation of cyclic oligomers (SnMe\(_{2}\))\(_{n}\) (5; n=5-8) in high yield was observed. These cyclic oligomers were also obtained from the controlled decomposition of cAAC\(^{Me}\)H-SnHMe\(_{2}\) (3).}, language = {en} } @article{CataldiRaschigGutmannetal.2023, author = {Cataldi, Eleonora and Raschig, Martina and Gutmann, Marcus and Geppert, Patrick T. and Ruopp, Matthias and Schock, Marvin and Gerwe, Hubert and Bertermann, R{\"u}diger and Meinel, Lorenz and Finze, Maik and Nowak-Kr{\´o}l, Agnieszka and Decker, Michael and L{\"u}hmann, Tessa}, title = {Amber Light Control of Peptide Secondary Structure by a Perfluoroaromatic Azobenzene Photoswitch}, series = {ChemBioChem}, volume = {24}, journal = {ChemBioChem}, number = {5}, doi = {10.1002/cbic.202200570}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312480}, year = {2023}, abstract = {The incorporation of photoswitches into the molecular structure of peptides and proteins enables their dynamic photocontrol in complex biological systems. Here, a perfluorinated azobenzene derivative triggered by amber light was site-specifically conjugated to cysteines in a helical peptide by perfluoroarylation chemistry. In response to the photoisomerization (trans→cis) of the conjugated azobenzene with amber light, the secondary structure of the peptide was modulated from a disorganized into an amphiphilic helical structure.}, language = {en} } @article{WeiserCuiDewhurstetal.2023, author = {Weiser, Jonas and Cui, Jingjing and Dewhurst, Rian D. and Braunschweig, Holger and Engels, Bernd and Fantuzzi, Felipe}, title = {Structure and bonding of proximity-enforced main-group dimers stabilized by a rigid naphthyridine diimine ligand}, series = {Journal of Computational Chemistry}, volume = {44}, journal = {Journal of Computational Chemistry}, number = {3}, doi = {10.1002/jcc.26994}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312586}, pages = {456 -- 467}, year = {2023}, abstract = {The development of ligands capable of effectively stabilizing highly reactive main-group species has led to the experimental realization of a variety of systems with fascinating properties. In this work, we computationally investigate the electronic, structural, energetic, and bonding features of proximity-enforced group 13-15 homodimers stabilized by a rigid expanded pincer ligand based on the 1,8-naphthyridine (napy) core. We show that the redox-active naphthyridine diimine (NDI) ligand enables a wide variety of structural motifs and element-element interaction modes, the latter ranging from isolated, element-centered lone pairs (e.g., E = Si, Ge) to cases where through-space π bonds (E = Pb), element-element multiple bonds (E = P, As) and biradical ground states (E = N) are observed. Our results hint at the feasibility of NDI-E2 species as viable synthetic targets, highlighting the versatility and potential applications of napy-based ligands in main-group chemistry.}, language = {en} } @article{LindlLamprechtArrowsmithetal.2023, author = {Lindl, Felix and Lamprecht, Anna and Arrowsmith, Merle and Khitro, Eugen and Rempel, Anna and Dietz, Maximilian and Wellnitz, Tim and B{\´e}langer-Chabot, Guillaume and Stoy, Andreas and Paprocki, Valerie and Prieschl, Dominik and Lenczyk, Carsten and Ramler, Jacqueline and Lichtenberg, Crispin and Braunschweig, Holger}, title = {Aromatic 1,2-Azaborinin-1-yls as Electron-Withdrawing Anionic Nitrogen Ligands for Main Group Elements}, series = {Chemistry - A European Journal}, volume = {29}, journal = {Chemistry - A European Journal}, number = {11}, doi = {10.1002/chem.202203345}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312222}, year = {2023}, abstract = {The 2-aryl-3,4,5,6-tetraphenyl-1,2-azaborinines 1-EMe\(_{3}\) and 2-EMe\(_{3}\) (E=Si, Sn; aryl=Ph (1), Mes (=2,4,6-trimethylphenyl, 2)) were synthesized by ring-expansion of borole precursors with N\(_{3}\)EMe\(_{3}\)-derived nitrenes. Desilylative hydrolysis of 1- and 2-SiMe\(_{3}\) yielded the corresponding N-protonated azaborinines, which were deprotonated with nBuLi or MN(SiMe\(_{3}\))\(_{2}\) (M=Na, K) to the corresponding group 1 salts, 1-M and 2-M. While the lithium salts crystallized as monomeric Lewis base adducts, the potassium salts formed coordination polymers or oligomers via intramolecular K⋅⋅⋅aryl π interactions. The reaction of 1-M or 2-M with CO\(_{2}\) yielded N-carboxylate salts, which were derivatized by salt metathesis to methyl and silyl esters. Salt metathesis of 1-M or 2-M with methyl triflate, [Cp*BeCl] (Cp*=C\(_{5}\)Me\(_{5}\)), BBr\(_{2}\)Ar (Ar=Ph, Mes, 2-thienyl), ECl\(_{3}\) (E=B, Al, Ga) and PX\(_{3}\) (X=Cl, Br) afforded the respective group 2, 13 and 15 1,2-azaborinin-2-yl complexes. Salt metathesis of 1-K with BBr\(_{3}\) resulted not only in N-borylation but also Ph-Br exchange between the endocyclic and exocyclic boron atoms. Solution \(^{11}\)B NMR data suggest that the 1,2-azaborinin-2-yl ligand is similarly electron-withdrawing to a bromide. In the solid state the endocyclic bond length alternation and the twisting of the C\(_{4}\)BN ring increase with the sterics of the substituents at the boron and nitrogen atoms, respectively. Regression analyses revealed that the downfield shift of the endocyclic \(^{11}\)B NMR resonances is linearly correlated to both the degree of twisting of the C\(_{4}\)BN ring and the tilt angle of the N-substituent. Calculations indicate that the 1,2-azaborinin-1-yl ligand has no sizeable π-donor ability and that the aromaticity of the ring can be subtly tuned by the electronics of the N-substituent.}, language = {en} } @article{KaltdorfBreitenbachKarletal.2023, author = {Kaltdorf, Martin and Breitenbach, Tim and Karl, Stefan and Fuchs, Maximilian and Kessie, David Komla and Psota, Eric and Prelog, Martina and Sarukhanyan, Edita and Ebert, Regina and Jakob, Franz and Dandekar, Gudrun and Naseem, Muhammad and Liang, Chunguang and Dandekar, Thomas}, title = {Software JimenaE allows efficient dynamic simulations of Boolean networks, centrality and system state analysis}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-27098-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313303}, year = {2023}, abstract = {The signal modelling framework JimenaE simulates dynamically Boolean networks. In contrast to SQUAD, there is systematic and not just heuristic calculation of all system states. These specific features are not present in CellNetAnalyzer and BoolNet. JimenaE is an expert extension of Jimena, with new optimized code, network conversion into different formats, rapid convergence both for system state calculation as well as for all three network centralities. It allows higher accuracy in determining network states and allows to dissect networks and identification of network control type and amount for each protein with high accuracy. Biological examples demonstrate this: (i) High plasticity of mesenchymal stromal cells for differentiation into chondrocytes, osteoblasts and adipocytes and differentiation-specific network control focusses on wnt-, TGF-beta and PPAR-gamma signaling. JimenaE allows to study individual proteins, removal or adding interactions (or autocrine loops) and accurately quantifies effects as well as number of system states. (ii) Dynamical modelling of cell-cell interactions of plant Arapidopsis thaliana against Pseudomonas syringae DC3000: We analyze for the first time the pathogen perspective and its interaction with the host. We next provide a detailed analysis on how plant hormonal regulation stimulates specific proteins and who and which protein has which type and amount of network control including a detailed heatmap of the A.thaliana response distinguishing between two states of the immune response. (iii) In an immune response network of dendritic cells confronted with Aspergillus fumigatus, JimenaE calculates now accurately the specific values for centralities and protein-specific network control including chemokine and pattern recognition receptors.}, language = {en} } @article{StegmannAndreattaWieser2023, author = {Stegmann, Yannik and Andreatta, Marta and Wieser, Matthias J.}, title = {The effect of inherently threatening contexts on visuocortical engagement to conditioned threat}, series = {Psychophysiology}, volume = {60}, journal = {Psychophysiology}, number = {4}, doi = {10.1111/psyp.14208}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312465}, year = {2023}, abstract = {Fear and anxiety are crucial for adaptive responding in life-threatening situations. Whereas fear is a phasic response to an acute threat accompanied by selective attention, anxiety is characterized by a sustained feeling of apprehension and hypervigilance during situations of potential threat. In the current literature, fear and anxiety are usually considered mutually exclusive, with partially separated neural underpinnings. However, there is accumulating evidence that challenges this distinction between fear and anxiety, and simultaneous activation of fear and anxiety networks has been reported. Therefore, the current study experimentally tested potential interactions between fear and anxiety. Fifty-two healthy participants completed a differential fear conditioning paradigm followed by a test phase in which the conditioned stimuli were presented in front of threatening or neutral contextual images. To capture defense system activation, we recorded subjective (threat, US-expectancy), physiological (skin conductance, heart rate) and visuocortical (steady-state visual evoked potentials) responses to the conditioned stimuli as a function of contextual threat. Results demonstrated successful fear conditioning in all measures. In addition, threat and US-expectancy ratings, cardiac deceleration, and visuocortical activity were enhanced for fear cues presented in threatening compared with neutral contexts. These results are in line with an additive or interactive rather than an exclusive model of fear and anxiety, indicating facilitated defensive behavior to imminent danger in situations of potential threat.}, language = {en} } @article{StegmannAndreattaPaulietal.2023, author = {Stegmann, Yannik and Andreatta, Marta and Pauli, Paul and Keil, Andreas and Wieser, Matthias J.}, title = {Investigating sustained attention in contextual threat using steady-state VEPs evoked by flickering video stimuli}, series = {Psychophysiology}, volume = {60}, journal = {Psychophysiology}, number = {5}, doi = {10.1111/psyp.14229}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312430}, year = {2023}, abstract = {Anxiety is characterized by anxious anticipation and heightened vigilance to uncertain threat. However, if threat is not reliably indicated by a specific cue, the context in which threat was previously experienced becomes its best predictor, leading to anxiety. A suitable means to induce anxiety experimentally is context conditioning: In one context (CTX+), an unpredictable aversive stimulus (US) is repeatedly presented, in contrast to a second context (CTX-), in which no US is ever presented. In this EEG study, we investigated attentional mechanisms during acquisition and extinction learning in 38 participants, who underwent a context conditioning protocol. Flickering video stimuli (32 s clips depicting virtual offices representing CTX+/-) were used to evoke steady-state visual evoked potentials (ssVEPs) as an index of visuocortical engagement with the contexts. Analyses of the electrocortical responses suggest a successful induction of the ssVEP signal by video presentation in flicker mode. Furthermore, we found clear indices of context conditioning and extinction learning on a subjective level, while cortical processing of the CTX+ was unexpectedly reduced during video presentation. The differences between CTX+ and CTX- diminished during extinction learning. Together, these results indicate that the dynamic sensory input of the video presentation leads to disruptions in the ssVEP signal, which is greater for motivationally significant, threatening contexts.}, language = {en} } @article{DanielLauthRothfuss2023, author = {Daniel, Antje and Lauth, Hans-Joachim and Rothfuß, Eberhard}, title = {Local Self-Governance and Weak Statehood: A Convincing Liaison?}, series = {Politics and Governance}, volume = {11}, journal = {Politics and Governance}, number = {2}, issn = {2183-2463}, doi = {10.17645/pag.v11i2.7166}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321149}, pages = {272-279}, year = {2023}, abstract = {This thematic issue addresses the relationship between local self-governance and the state. Self-governance is understood as the rules that emerge in the local social and spatial context. Local self-governance of individual local groups, actors, communities, and their social and institutional arrangements are considered. From this situated collective entanglement, the interactions and relations with state authorities are analysed in the various contributions embedded in local contexts of different world regions and based on empirical social science research containing mostly interdisciplinary approaches. The nine case studies of this thematic issue reflect a variety of statehoods (weak to restrained), divers "intentionalities" of local self-governance (emancipatory and democratic, socio-economically, and socio-culturally oriented, security-driven or ecological), and their state-locality entanglements range between four forms of relationships: mutually supportive, conflictual, ambivalent, and avoiding.}, language = {en} } @article{RinnKrishnaDeutsch2023, author = {Rinn, Robin and Krishna, Anand and Deutsch, Roland}, title = {The psychology of income wealth threshold estimations: A registered report}, series = {British Journal of Social Psychology}, volume = {62}, journal = {British Journal of Social Psychology}, number = {1}, doi = {10.1111/bjso.12581}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311847}, pages = {630 -- 650}, year = {2023}, abstract = {How do people estimate the income that is needed to be rich? Two correlative survey studies (Study 1 and 2, N = 568) and one registered experimental study (Study 3, N = 500) examined the cognitive mechanisms that are used to derive an answer to this question. We tested whether individuals use their personal income (PI) as a self-generated anchor to derive an estimate of the income needed to be rich (= income wealth threshold estimation, IWTE). On a bivariate level, we found the expected positive relationship between one's PI and IWTE and, in line with previous findings, we found that people do not consider themselves rich. Furthermore, we predicted that individuals additionally use information about their social status within their social circles to make an IWTE. The findings from study 2 support this notion and show that only self-reported high-income individuals show different IWTEs depending on relative social status: Individuals in this group who self-reported a high status produced higher IWTEs than individuals who self-reported low status. The registered experimental study could not replicate this pattern robustly, although the results trended non-significantly in the same direction. Together, the findings revealed that the income of individuals as well as the social environment are used as sources of information to make IWTE judgements, although they are likely not the only important predictors.}, language = {en} } @article{kleinSelleSuchotzkiPertzovetal.2023, author = {klein Selle, Nathalie and Suchotzki, Kristina and Pertzov, Yoni and Gamer, Matthias}, title = {Orienting versus inhibition: The theory behind the ocular-based Concealed Information Test}, series = {Psychophysiology}, volume = {60}, journal = {Psychophysiology}, number = {3}, doi = {10.1111/psyp.14186}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312626}, year = {2023}, abstract = {When trying to conceal one's knowledge, various ocular changes occur. However, which cognitive mechanisms drive these changes? Do orienting or inhibition—two processes previously associated with autonomic changes—play a role? To answer this question, we used a Concealed Information Test (CIT) in which participants were either motivated to conceal (orienting + inhibition) or reveal (orienting only) their knowledge. While pupil size increased in both motivational conditions, the fixation and blink CIT effects were confined to the conceal condition. These results were mirrored in autonomic changes, with skin conductance increasing in both conditions while heart rate decreased solely under motivation to conceal. Thus, different cognitive mechanisms seem to drive ocular responses. Pupil size appears to be linked to the orienting of attention (akin to skin conductance changes), while fixations and blinks rather seem to reflect arousal inhibition (comparable to heart rate changes). This knowledge strengthens CIT theory and illuminates the relationship between ocular and autonomic activity.}, language = {en} } @article{LudwigStrack2023, author = {Ludwig, Jonas and Strack, Fritz}, title = {Asymmetrical friendships? People are willing to risk COVID-19 infection from friends but are reluctant to pass it on to them}, series = {Journal of Applied Social Psychology}, volume = {53}, journal = {Journal of Applied Social Psychology}, number = {1}, doi = {10.1111/jasp.12927}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312411}, pages = {69 -- 79}, year = {2023}, abstract = {Although most protective behaviors related to the COVID-19 pandemic come with personal costs, they will produce the largest benefit if everybody cooperates. This study explores two interacting factors that drive cooperation in this tension between private and collective interests. A preregistered experiment (N = 299) examined (a) how the quality of the relation among interacting partners (social proximity), and (b) how focusing on the risk of self-infection versus onward transmission affected intentions to engage in protective behaviors. The results suggested that risk focus was an important moderator of the relation between social proximity and protection intentions. Specifically, participants were more willing to accept the risk of self-infection from close others than from strangers, resulting in less caution toward a friend than toward a distant other. However, when onward transmission was the primary concern, participants were more reluctant to effect transmission to close others, resulting in more caution toward friends than strangers. These findings inform the debate about effective nonclinical measures against the pandemic. Practical implications for risk communication are discussed.}, language = {en} } @article{SchadtIsraelBeezetal.2023, author = {Schadt, Fabian and Israel, Ina and Beez, Alexandra and Alushi, Kastriot and Weiland, Judith and Ernestus, Ralf-Ingo and Westermaier, Thomas and Samnick, Samuel and Lilla, Nadine}, title = {Analysis of cerebral glucose metabolism following experimental subarachnoid hemorrhage over 7 days}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-26183-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300725}, year = {2023}, abstract = {Little is known about changes in brain metabolism following SAH, possibly leading towards secondary brain damage. Despite sustained progress in the last decade, analysis of in vivo acquired data still remains challenging. The present interdisciplinary study uses a semi-automated data analysis tool analyzing imaging data independently from the administrated radiotracer. The uptake of 2-[18F]Fluoro-2-deoxy-glucose ([\(^{18}\)F]FDG) was evaluated in different brain regions in 14 male Sprague-Dawley rats, randomized into two groups: (1) SAH induced by the endovascular filament model and (2) sham operated controls. Serial [\(^{18}\)F]FDG-PET measurements were carried out. Quantitative image analysis was performed by uptake ratio using a self-developed MRI-template based data analysis tool. SAH animals showed significantly higher [\(^{18}\)F]FDG accumulation in gray matter, neocortex and olfactory system as compared to animals of the sham group, while white matter and basal forebrain region showed significant reduced tracer accumulation in SAH animals. All significant metabolic changes were visualized from 3 h, over 24 h (day 1), day 4 and day 7 following SAH/sham operation. This [\(^{18}\)F]FDG-PET study provides important insights into glucose metabolism alterations following SAH—for the first time in different brain regions and up to day 7 during course of disease.}, language = {en} } @article{WitteArrowsmithLamprechtetal.2023, author = {Witte, Robert and Arrowsmith, Merle and Lamprecht, Anna and Schorr, Fabian and Krummenacher, Ivo and Braunschweig, Holger}, title = {C-C and C-N Bond Activation, Lewis-Base Coordination and One- and Two-Electron Oxidation at a Linear Aminoborylene}, series = {Chemistry - A European Journal}, volume = {29}, journal = {Chemistry - A European Journal}, number = {16}, doi = {10.1002/chem.202203663}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312491}, year = {2023}, abstract = {A cyclic alkyl(amino)carbene (CAAC)-stabilized dicoordinate aminoborylene is synthesized by the twofold reduction of a [(CAAC)BCl\(_{2}\)(TMP)] (TMP=2,6-tetramethylpiperidyl) precursor. NMR-spectroscopic, X-ray crystallographic and computational analyses confirm the cumulenic nature of the central C=B=N moiety. Irradiation of [(CAAC)B(TMP)] (2) resulted in an intramolecular C-C bond activation, leading to a doubly-fused C\(_{10}\)BN heterocycle, while the reaction with acetonitrile resulted in an aryl migration from the CAAC to the acetonitrile nitrogen atom, concomitant with tautomerization of the latter to a boron-bound allylamino ligand. One-electron oxidation of 2 with CuX (X=Cl, Br) afforded the corresponding amino(halo)boryl radicals, which were characterized by EPR spectroscopy and DFT calculations. Placing 2 under an atmosphere of CO afforded the tricoordinate (CAAC,CO)-stabilized aminoborylene. Finally, the twofold oxidation of 2 with chalcogens led, in the case of N\(_{2}\)O and sulfur, to the splitting of the B-C\(_{CAAC}\) bond and formation of the 2,4-diamino-1,3,2,4-dichalcogenadiboretanes and CAAC-chalcogen adducts, whereas with selenium a monomeric boraselenone was isolated, which showed some degree of B-Se multiple bonding.}, language = {en} } @article{BruecknerRitschelJimenez‐Hallaetal.2023, author = {Br{\"u}ckner, Tobias and Ritschel, Benedikt and Jim{\´e}nez-Halla, J. Oscar C. and Fantuzzi, Felipe and Duwe, Dario and Markl, Christian and Dewhurst, Rian D. and Dietz, Maximilian and Braunschweig, Holger}, title = {Metal-Free Intermolecular C-H Borylation of N-Heterocycles at B-B Multiple Bonds}, series = {Angewandte Chemie International Edition}, volume = {62}, journal = {Angewandte Chemie International Edition}, number = {5}, doi = {10.1002/anie.202213284}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312385}, year = {2023}, abstract = {Carbene-stabilized diborynes of the form LBBL (L=N-heterocyclic carbene (NHC) or cyclic alkyl(amino)carbene (CAAC)) induce rapid, high yielding, intermolecular ortho-C-H borylation at N-heterocycles at room temperature. A simple pyridyldiborene is formed when an NHC-stabilized diboryne is combined with pyridine, while a CAAC-stabilized diboryne leads to activation of two pyridine molecules to give a tricyclic alkylideneborane, which can be forced to undergo a further H-shift resulting in a zwitterionic, doubly benzo-fused 1,3,2,5-diazadiborinine by heating. Use of the extended N-heteroaromatic quinoline leads to a borylmethyleneborane under mild conditions via an unprecedented boron-carbon exchange process.}, language = {en} } @article{ThieleRichterHilger2023, author = {Thiele, Jonas A. and Richter, Aylin and Hilger, Kirsten}, title = {Multimodal brain signal complexity predicts human intelligence}, series = {eNeuro}, volume = {10}, journal = {eNeuro}, number = {2}, doi = {10.1523/ENEURO.0345-22.2022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312949}, year = {2023}, abstract = {Spontaneous brain activity builds the foundation for human cognitive processing during external demands. Neuroimaging studies based on functional magnetic resonance imaging (fMRI) identified specific characteristics of spontaneous (intrinsic) brain dynamics to be associated with individual differences in general cognitive ability, i.e., intelligence. However, fMRI research is inherently limited by low temporal resolution, thus, preventing conclusions about neural fluctuations within the range of milliseconds. Here, we used resting-state electroencephalographical (EEG) recordings from 144 healthy adults to test whether individual differences in intelligence (Raven's Advanced Progressive Matrices scores) can be predicted from the complexity of temporally highly resolved intrinsic brain signals. We compared different operationalizations of brain signal complexity (multiscale entropy, Shannon entropy, Fuzzy entropy, and specific characteristics of microstates) regarding their relation to intelligence. The results indicate that associations between brain signal complexity measures and intelligence are of small effect sizes (r ∼ 0.20) and vary across different spatial and temporal scales. Specifically, higher intelligence scores were associated with lower complexity in local aspects of neural processing, and less activity in task-negative brain regions belonging to the default-mode network. Finally, we combined multiple measures of brain signal complexity to show that individual intelligence scores can be significantly predicted with a multimodal model within the sample (10-fold cross-validation) as well as in an independent sample (external replication, N = 57). In sum, our results highlight the temporal and spatial dependency of associations between intelligence and intrinsic brain dynamics, proposing multimodal approaches as promising means for future neuroscientific research on complex human traits.}, language = {en} } @article{NollGrossShoyamaetal.2023, author = {Noll, Niklas and Groß, Tobias and Shoyama, Kazutaka and Beuerle, Florian and W{\"u}rthner, Frank}, title = {Folding-Induced Promotion of Proton-Coupled Electron Transfers via Proximal Base for Light-Driven Water Oxidation}, series = {Angewandte Chemie International Edition}, volume = {62}, journal = {Angewandte Chemie International Edition}, number = {7}, doi = {10.1002/anie.202217745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312020}, year = {2023}, abstract = {Proton-coupled electron-transfer (PCET) processes play a key role in biocatalytic energy conversion and storage, for example, photosynthesis or nitrogen fixation. Here, we report a series of bipyridine-containing di- to tetranuclear Ru(bda) macrocycles 2 C-4 C (bda: 2,2′-bipyridine-6,6′-dicarboxylate) to promote O-O bond formation. In photocatalytic water oxidation under neutral conditions, all complexes 2 C-4 C prevail in a folded conformation that support the water nucleophilic attack (WNA) pathway with remarkable turnover frequencies of up to 15.5 s\(^{-1}\) per Ru unit respectively. Single-crystal X-ray analysis revealed an increased tendency for intramolecular π-π stacking and preorganization of the proximal bases close to the active centers for the larger macrocycles. H/D kinetic isotope effect studies and electrochemical data demonstrate the key role of the proximal bipyridines as proton acceptors in lowering the activation barrier for the crucial nucleophilic attack of H\(_{2}\)O in the WNA mechanism.}, language = {en} } @article{PreitschopfSturmStroganovaetal.2023, author = {Preitschopf, Tobias and Sturm, Floriane and Stroganova, Iuliia and Lemmens, Alexander K. and Rijs, Anouk M. and Fischer, Ingo}, title = {IR/UV Double Resonance Study of the 2-Phenylallyl Radical and its Pyrolysis Products}, series = {Chemistry - A European Journal}, volume = {29}, journal = {Chemistry - A European Journal}, number = {13}, doi = {10.1002/chem.202202943}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312338}, year = {2023}, abstract = {Isolated 2-phenylallyl radicals (2-PA), generated by pyrolysis from a nitrite precursor, have been investigated by IR/UV ion dip spectroscopy using free electron laser radiation. 2-PA is a resonance-stabilized radical that is considered to be involved in the formation of polycyclic aromatic hydrocarbons (PAH) in combustion, but also in interstellar space. The radical is identified based on its gas-phase IR spectrum. Furthermore, a number of bimolecular reaction products are identified, showing that the self-reaction as well as reactions with unimolecular decomposition products of 2-PA form several PAH efficiently. Possible mechanisms are discussed and the chemistry of 2-PA is compared with the one of the related 2-methylallyl and phenylpropargyl radicals.}, language = {en} } @article{GrueneLondiGillettetal.2023, author = {Gr{\"u}ne, Jeannine and Londi, Giacomo and Gillett, Alexander J. and St{\"a}hly, Basil and Lulei, Sebastian and Kotova, Maria and Olivier, Yoann and Dyakonov, Vladimir and Sperlich, Andreas}, title = {Triplet Excitons and Associated Efficiency-Limiting Pathways in Organic Solar Cell Blends Based on (Non-) Halogenated PBDB-T and Y-Series}, series = {Advanced Functional Materials}, volume = {33}, journal = {Advanced Functional Materials}, number = {12}, doi = {10.1002/adfm.202212640}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312164}, year = {2023}, abstract = {The great progress in organic photovoltaics (OPV) over the past few years has been largely achieved by the development of non-fullerene acceptors (NFAs), with power conversion efficiencies now approaching 20\%. To further improve device performance, loss mechanisms must be identified and minimized. Triplet states are known to adversely affect device performance, since they can form energetically trapped excitons on low-lying states that are responsible for non-radiative losses or even device degradation. Halogenation of OPV materials has long been employed to tailor energy levels and to enhance open circuit voltage. Yet, the influence on recombination to triplet excitons has been largely unexplored. Using the complementary spin-sensitive methods of photoluminescence detected magnetic resonance and transient electron paramagnetic resonance corroborated by transient absorption and quantum-chemical calculations, exciton pathways in OPV blends are unravelled employing the polymer donors PBDB-T, PM6, and PM7 together with NFAs Y6 and Y7. All blends reveal triplet excitons on the NFA populated via non-geminate hole back transfer and, in blends with halogenated donors, also by spin-orbit coupling driven intersystem crossing. Identifying these triplet formation pathways in all tested solar cell absorber films highlights the untapped potential for improved charge generation to further increase plateauing OPV efficiencies.}, language = {en} } @article{Kestler2023, author = {Kestler, Thomas}, title = {Exploring the Relationship Between Social Movement Organizations and the State in Latin America}, series = {Politics and Governance}, volume = {11}, journal = {Politics and Governance}, number = {2}, issn = {2183-2463}, doi = {10.17645/pag.v11i2.6383}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321152}, pages = {346-356}, year = {2023}, abstract = {Under conditions of weak statehood, societal actors are supposed to assume functions usually attributed to the state. Social self-organization is expected to emerge when the state leaves important social problems unattended. Should social self-organization, therefore, be regarded as a reaction to state weakness and as compensation for state failure in the provision of basic services? Does society organize itself on its own in areas where the state is absent or ineffective? By the example of two Latin American social movements, this article aims to show that social self-organization—at least on a larger scale—is not independent of the state, but rather a result of a dynamic interaction with the state. The two examples this article explores are the middle-class Venezuelan neighborhood movement and the Argentine piquetero movement of unemployed workers. Both movements emerged as reactions to the state's failure and retreat from essential social functions and both developed into extensive and influential social actors. For that reason, they can be regarded as crucial cases for observing the patterns and conditions of social self-organization and autonomous collective action within the specific Latin American context. Despite their different backgrounds and social bases, the two cases reveal remarkable similarities. They show that the emergence and development of self-organized social groups cannot be conceived simply as a reaction to state weakness, but rather should be viewed as a dynamic interaction with the state.}, language = {en} } @article{WeiWangYangetal.2023, author = {Wei, Yuxiang and Wang, Junyi and Yang, Weiguang and Lin, Zhenyang and Ye, Qing}, title = {Boosting Ring Strain and Lewis Acidity of Borirane: Synthesis, Reactivity and Density Functional Theory Studies of an Uncoordinated Arylborirane Fused to o-Carborane}, series = {Chemistry - A European Journal}, volume = {29}, journal = {Chemistry - A European Journal}, number = {5}, doi = {10.1002/chem.202203265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312089}, year = {2023}, abstract = {Among the parent borirane, benzoborirene and ortho-dicarbadodecaborane-fused borirane, the latter possesses the highest ring strain and the highest Lewis acidity according to our density functional theory (DFT) studies. The synthesis of this class of compounds is thus considerably challenging. The existing examples require either a strong π-donating group or an extra ligand for B-coordination, which nevertheless suppresses or completely turns off the Lewis acidity. The title compound, which possesses both features, not only allows the 1,2-insertion of P=O, C=O or C≡N to proceed under milder conditions, but also enables the heretofore unknown dearomative 1,4-insertion of Ar-(C=O)- into a B-C bond. The fusion of strained molecular systems to an o-carborane cage shows great promise for boosting both the ring strain and acidity.}, language = {en} } @article{WeibelPoppReisetal.2023, author = {Weibel, Stephanie and Popp, Maria and Reis, Stefanie and Skoetz, Nicole and Garner, Paul and Sydenham, Emma}, title = {Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis}, series = {Research Synthesis Methods}, volume = {14}, journal = {Research Synthesis Methods}, number = {3}, doi = {10.1002/jrsm.1599}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318236}, pages = {357 -- 369}, year = {2023}, abstract = {Evidence synthesis findings depend on the assumption that the included studies follow good clinical practice and results are not fabricated or false. Studies which are problematic due to scientific misconduct, poor research practice, or honest error may distort evidence synthesis findings. Authors of evidence synthesis need transparent mechanisms to identify and manage problematic studies to avoid misleading findings. As evidence synthesis authors of the Cochrane COVID-19 review on ivermectin, we identified many problematic studies in terms of research integrity and regulatory compliance. Through iterative discussion, we developed a research integrity assessment (RIA) tool for randomized controlled trials for the update of this Cochrane review. In this paper, we explain the rationale and application of the RIA tool in this case study. RIA assesses six study criteria: study retraction, prospective trial registration, adequate ethics approval, author group, plausibility of methods (e.g., randomization), and plausibility of study results. RIA was used in the Cochrane review as part of the eligibility check during screening of potentially eligible studies. Problematic studies were excluded and studies with open questions were held in awaiting classification until clarified. RIA decisions were made independently by two authors and reported transparently. Using the RIA tool resulted in the exclusion of >40\% of studies in the first update of the review. RIA is a complementary tool prior to assessing "Risk of Bias" aiming to establish the integrity and authenticity of studies. RIA provides a platform for urgent development of a standard approach to identifying and managing problematic studies.}, language = {en} } @article{BellutBieberKraftetal.2023, author = {Bellut, Maximilian and Bieber, Michael and Kraft, Peter and Weber, Alexander N. R. and Stoll, Guido and Schuhmann, Michael K.}, title = {Delayed NLRP3 inflammasome inhibition ameliorates subacute stroke progression in mice}, series = {Journal of Neuroinflammation}, volume = {20}, journal = {Journal of Neuroinflammation}, number = {1}, doi = {10.1186/s12974-022-02674-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300599}, year = {2023}, abstract = {Background Ischemic stroke immediately evokes a strong neuro-inflammatory response within the vascular compartment, which contributes to primary infarct development under vessel occlusion as well as further infarct growth despite recanalization, referred to as ischemia/reperfusion injury. Later, in the subacute phase of stroke (beyond day 1 after recanalization), further inflammatory processes within the brain parenchyma follow. Whether this second wave of parenchymal inflammation contributes to an additional/secondary increase in infarct volumes and bears the potential to be pharmacologically targeted remains elusive. We addressed the role of the NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome in the subacute phase of ischemic stroke. Methods Focal cerebral ischemia was induced in C57Bl/6 mice by a 30-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with the NLRP3 inhibitor MCC950 therapeutically 24 h after or prophylactically before tMCAO. Stroke outcome, including infarct size and functional deficits as well as the local inflammatory response, was assessed on day 7 after tMCAO. Results Infarct sizes on day 7 after tMCAO decreased about 35\% after delayed and about 60\% after prophylactic NLRP3 inhibition compared to vehicle. Functionally, pharmacological inhibition of NLRP3 mitigated the local inflammatory response in the ischemic brain as indicated by reduction of infiltrating immune cells and reactive astrogliosis. Conclusions Our results demonstrate that the NLRP3 inflammasome continues to drive neuroinflammation within the subacute stroke phase. NLRP3 inflammasome inhibition leads to a better long-term outcome—even when administered with a delay of 1 day after stroke induction, indicating ongoing inflammation-driven infarct progression. These findings may pave the way for eagerly awaited delayed treatment options in ischemic stroke.}, language = {en} } @article{ParisiLehnerSchraderetal.2023, author = {Parisi, Sandra and Lehner, Nina and Schrader, Hanna and Kierer, Leonard and Fleischer, Anna and Miljukov, Olga and Borgulya, Gabor and R{\"u}ter, Gernot and Viniol, Annika and G{\´a}gyor, Ildik{\´o}}, title = {Experiencing COVID-19, home isolation and primary health care: A mixed-methods study}, series = {Frontiers in Public Health}, volume = {10}, journal = {Frontiers in Public Health}, issn = {2296-2565}, doi = {10.3389/fpubh.2022.1023431}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301498}, year = {2023}, abstract = {Objectives Although the vast majority of COVID-19 cases are treated in primary care, patients' experiences during home isolation have been little studied. This study aimed to explore the experiences of patients with acute COVID-19 and to identify challenges after the initial adaptation of the German health system to the pandemic (after first infection wave from February to June 2020). Methods A mixed-method convergent design was used to gain a holistic insight into patients experience. The study consisted of a cross-sectional survey, open survey answers and semi-structured telephone interviews. Descriptive analysis was performed on quantitative survey answers. Between group differences were calculated to explore changes after the first infection wave. Qualitative thematic analysis was conducted on open survey answers and interviews. The results were then compared within a triangulation protocol. Results A total of 1100 participants from all German states were recruited by 145 general practitioners from August 2020 to April 2021, 42 additionally took part in qualitative interviews. Disease onset varied from February 2020 to April 2021. After the first infection wave, more participants were tested positive during the acute disease (88.8\%; 95.2\%; P < 0.001). Waiting times for tests (mean 4.5 days, SD 4.1; 2.7days, SD 2.6, P < 0.001) and test results (mean 2.4 days, SD 1.9; 1.8 days, SD 1.3, P < 0.001) decreased. Qualitative results indicated that the availability of repeated testing and antigen tests reduced insecurities, transmission and related guilt. Although personal consultations at general practices increased (6.8\%; 15.5\%, P < 0.001), telephone consultation remained the main mode of consultation (78.5\%) and video remained insignificant (1.9\%). The course of disease, the living situation and social surroundings during isolation, access to health care, personal resilience, spirituality and feelings of guilt and worries emerged as themes influencing the illness experience. Challenges were contact management and adequate provision of care during home isolation. A constant contact person within the health system helped against feelings of care deprivation, uncertainty and fear. Conclusions Our study highlights that home isolation of individuals with COVID-19 requires a holistic approach that considers all aspects of patient care and effective coordination between different care providers.}, language = {en} } @article{SoundararajanMarincolaLiongetal.2023, author = {Soundararajan, Manonmani and Marincola, Gabriella and Liong, Olivia and Marciniak, Tessa and Wencker, Freya D. R. and Hofmann, Franka and Schollenbruch, Hannah and Kobusch, Iris and Linnemann, Sabrina and Wolf, Silver A. and Helal, Mustafa and Semmler, Torsten and Walther, Birgit and Schoen, Christoph and Nyasinga, Justin and Revathi, Gunturu and Boelhauve, Marc and Ziebuhr, Wilma}, title = {Farming practice influences antimicrobial resistance burden of non-aureus staphylococci in pig husbandries}, series = {Microorganisms}, volume = {11}, journal = {Microorganisms}, number = {1}, issn = {2076-2607}, doi = {10.3390/microorganisms11010031}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312750}, year = {2023}, abstract = {Non-aureus staphylococci (NAS) are ubiquitous bacteria in livestock-associated environments where they may act as reservoirs of antimicrobial resistance (AMR) genes for pathogens such as Staphylococcus aureus. Here, we tested whether housing conditions in pig farms could influence the overall AMR-NAS burden. Two hundred and forty porcine commensal and environmental NAS isolates from three different farm types (conventional, alternative, and organic) were tested for phenotypic antimicrobial susceptibility and subjected to whole genome sequencing. Genomic data were analysed regarding species identity and AMR gene carriage. Seventeen different NAS species were identified across all farm types. In contrast to conventional farms, no AMR genes were detectable towards methicillin, aminoglycosides, and phenicols in organic farms. Additionally, AMR genes to macrolides and tetracycline were rare among NAS in organic farms, while such genes were common in conventional husbandries. No differences in AMR detection existed between farm types regarding fosfomycin, lincosamides, fusidic acid, and heavy metal resistance gene presence. The combined data show that husbandry conditions influence the occurrence of resistant and multidrug-resistant bacteria in livestock, suggesting that changing husbandry practices may be an appropriate means of limiting the spread of AMR bacteria on farms.}, language = {en} } @article{MichauxGerovacHansenetal.2023, author = {Michaux, Charlotte and Gerovac, Milan and Hansen, Elisabeth E. and Barquist, Lars and Vogel, J{\"o}rg}, title = {Grad-seq analysis of Enterococcus faecalis and Enterococcus faecium provides a global view of RNA and protein complexes in these two opportunistic pathogens}, series = {microLife}, volume = {4}, journal = {microLife}, doi = {10.1093/femsml/uqac027}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313311}, year = {2023}, abstract = {Enterococcus faecalis and Enterococcus faecium are major nosocomial pathogens. Despite their relevance to public health and their role in the development of bacterial antibiotic resistance, relatively little is known about gene regulation in these species. RNA-protein complexes serve crucial functions in all cellular processes associated with gene expression, including post-transcriptional control mediated by small regulatory RNAs (sRNAs). Here, we present a new resource for the study of enterococcal RNA biology, employing the Grad-seq technique to comprehensively predict complexes formed by RNA and proteins in E. faecalis V583 and E. faecium AUS0004. Analysis of the generated global RNA and protein sedimentation profiles led to the identification of RNA-protein complexes and putative novel sRNAs. Validating our data sets, we observe well-established cellular RNA-protein complexes such as the 6S RNA-RNA polymerase complex, suggesting that 6S RNA-mediated global control of transcription is conserved in enterococci. Focusing on the largely uncharacterized RNA-binding protein KhpB, we use the RIP-seq technique to predict that KhpB interacts with sRNAs, tRNAs, and untranslated regions of mRNAs, and might be involved in the processing of specific tRNAs. Collectively, these datasets provide departure points for in-depth studies of the cellular interactome of enterococci that should facilitate functional discovery in these and related Gram-positive species. Our data are available to the community through a user-friendly Grad-seq browser that allows interactive searches of the sedimentation profiles (https://resources.helmholtz-hiri.de/gradseqef/).}, language = {en} } @article{RaschigRamirez‐ZavalaWiestetal.2023, author = {Raschig, Martina and Ram{\´i}rez-Zavala, Bernardo and Wiest, Johannes and Saedtler, Marco and Gutmann, Marcus and Holzgrabe, Ulrike and Morschh{\"a}user, Joachim and Meinel, Lorenz}, title = {Azobenzene derivatives with activity against drug-resistant Candida albicans and Candida auris}, series = {Archiv der Pharmazie}, volume = {356}, journal = {Archiv der Pharmazie}, number = {2}, doi = {10.1002/ardp.202200463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312295}, year = {2023}, abstract = {Increasing resistance against antimycotic drugs challenges anti-infective therapies today and contributes to the mortality of infections by drug-resistant Candida species and strains. Therefore, novel antifungal agents are needed. A promising approach in developing new drugs is using naturally occurring molecules as lead structures. In this work, 4,4'-dihydroxyazobenzene, a compound structurally related to antifungal stilbene derivatives and present in Agaricus xanthodermus (yellow stainer), served as a starting point for the synthesis of five azobenzene derivatives. These compounds prevented the growth of both fluconazole-susceptible and fluconazole-resistant Candida albicans and Candida auris strains. Further in vivo studies are required to confirm the potential therapeutic value of these compounds.}, language = {en} } @article{LassmannEberlein2023, author = {Lassmann, Michael and Eberlein, Uta}, title = {Comparing absorbed doses and radiation risk of the α-emitting bone-seekers [\(^{223}\)Ra]RaCl\(_2\) and [\(^{224}\)Ra]RaCl\(_2\)}, series = {Frontiers in Medicine}, volume = {9}, journal = {Frontiers in Medicine}, issn = {2296-858X}, doi = {10.3389/fmed.2022.1057373}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301509}, year = {2023}, abstract = {[\(^{223}\)Ra]RaCl\(_2\) and [\(^{224}\)Ra]RaCl\(_2\) are bone seekers, emitting high LET, and short range (< 100 μm) alpha-particles. Both radionuclides show similar decay properties; the total alpha energies are comparable (\(^{223}\)Ra: ≈28 MeV, \(^{224}\)Ra: ≈26 MeV). [\(^{224}\)Ra]RaCl\(_2\) has been used from the mid-1940s until 1990 for treating different bone and joint diseases with activities of up to approximately 50 MBq [\(^{224}\)Ra]RaCl\(_2\). In 2013 [\(^{223}\)Ra]RaCl\(_2\) obtained marketing authorization by the FDA and by the European Union for the treatment of metastatic prostate cancer with an activity to administer of 0.055 MBq per kg body weight for six cycles. For intravenous injections in humans a model calculation using the biokinetic model of ICRP67 shows a ratio of organ absorbed dose coefficients (\(^{224}\)Ra:\(^{223}\)Ra) between 0.37 (liver) and 0.97 except for the kidneys (2.27) and blood (1.57). For the red marrow as primary organ-at-risk, the ratio is 0.57. The differences are mainly caused be the differing half-lives of the decay products of both radium isotopes. Both radionuclides show comparable DNA damage patterns in peripheral blood mononuclear cells after internal ex-vivo irradiation. Data on the long-term radiation-associated side effects are only available for treatment with [\(^{224}\)Ra]RaCl\(_2\). Two epidemiological studies followed two patient groups treated with [\(^{224}\)Ra]RaCl\(_2\) for more than 25 years. One of them was the "Spiess study", a cohort of 899 juvenile patients who received several injections of [\(^{224}\)Ra]RaCl\(_2\) with a mean specific activity of 0.66 MBq/kg. Another patient group of ankylosing spondylitis patients was treated with 10 repeated intravenous injections of [\(^{224}\)Ra]RaCl\(_2\), 1 MBq each, 1 week apart. In total 1,471 of these patients were followed-up in the "Wick study". In both studies, an increased cancer mortality by leukemia and solid cancers was observed. Similar considerations on long-term effects likely apply to [\(^{223}\)Ra]RaCl\(_2\) as well since the biokinetics are similar and the absorbed doses in the same range. However, this increased risk will most likely not be observed due to the much shorter life expectancy of prostate cancer patients treated with [\(^{223}\)Ra]RaCl\(_2\).}, language = {en} } @article{AlpermannMalzer2023, author = {Alpermann, Bj{\"o}rn and Malzer, Michael}, title = {"In Other News": China's International Media Strategy on Xinjiang — CGTN and New China TV on YouTube}, series = {Modern China}, journal = {Modern China}, edition = {Online first}, issn = {1552-6836}, doi = {10.1177/00977004231169008}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314173}, pages = {1-44}, year = {2023}, abstract = {In the Western world China stands accused of severe human rights violations regarding its treatment of the Uyghurs and other predominantly Muslim minorities in its northwestern Xinjiang Uyghur Autonomous Region. This is the first article to systematically analyze the response of China's international state media to these allegations. By studying the YouTube channels of two leading Chinese state media, China Global Television Network (CGTN) and New China TV (operated by Xinhua News Agency), it presents an indepth understanding of how China's foreign-facing propaganda works in a crucial case. The quantitative content analysis highlights how China reacted to increasing international (mostly United States) pressure regarding its Xinjiang policies by producing higher volumes of videos and putting out new counternarratives. The qualitative analysis that follows provides in-depth treatment of the most important discourses that Chinese media engage in to salvage the nation's international image, namely those on development, culture, nature, and terrorism. It finds several ways of countering criticism, ranging from presenting a positive image of China, in line with traditional propaganda guidelines and President Xi Jinping's assignment to state media to "tell the China story well," to more innovative approaches. Thus the development narrative becomes more personalized, the discourse on culture supports the "heritagization process" to incorporate minority cultures into a harmonized "Chinese civilization," representations of nature firmly tie Xinjiang into the discourse of "beautiful China," the "terror narrative" strategically employs shocking footage in an attempt to gain international "discourse power," etc. The article provides an up-to-date picture of China's state media strategy on a highly contentious international issue.}, language = {en} } @article{BrustNaglerShoyamaetal.2023, author = {Brust, Felix and Nagler, Oliver and Shoyama, Kazutaka and Stolte, Matthias and W{\"u}rthner, Frank}, title = {Organic Light-Emitting Diodes Based on Silandiol-Bay-Bridged Perylene Bisimides}, series = {Advanced Optical Materials}, volume = {11}, journal = {Advanced Optical Materials}, number = {5}, doi = {10.1002/adom.202202676}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312599}, year = {2023}, abstract = {Perylene bisimides (PBIs) are among the best fluorophores but have to be enwrapped for optoelectronic applications by large and heavy substituents to prevent their ππ-stacking, which is known to accelerate non-radiative decay processes in the solid state. Here, light-weight di-tert-butylsilyl groups are introduced to bridge 1,12-dihydroxy and 1,6,7,12-tetrahydroxy PBIs to afford sublimable dyes for vacuum-processed optoelectronic devices. For both new compounds, this substitution provides a twisted and shielded perylene π-core whose, via OSiObridges, rigid structure affords well-resolved absorption and emission spectra with strong fluorescence in solution, as well as in the solid state. The usefulness of these dyes for vacuum-processed optoelectronic devices is demonstrated in organic light-emitting diodes (OLEDs) that show monomer-like emission spectra and high maximum external quantum efficiency (EQEmax) values of up to 3.1\% for the doubly silicon-bridged PBI.}, language = {en} } @article{DresenPimientoPateletal.2023, author = {Dresen, Ellen and Pimiento, Jose M. and Patel, Jayshil J. and Heyland, Daren K. and Rice, Todd W. and Stoppe, Christian}, title = {Overview of oxidative stress and the role of micronutrients in critical illness}, series = {Journal of Parenteral and Enteral Nutrition}, volume = {47}, journal = {Journal of Parenteral and Enteral Nutrition}, doi = {10.1002/jpen.2421}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318186}, pages = {S38 -- S49}, year = {2023}, abstract = {Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness.}, language = {en} } @article{SteinerZacharyBaueretal.2023, author = {Steiner, Thomas and Zachary, Marie and Bauer, Susanne and M{\"u}ller, Martin J. and Krischke, Markus and Radziej, Sandra and Klepsch, Maximilian and Huettel, Bruno and Eisenreich, Wolfgang and Rudel, Thomas and Beier, Dagmar}, title = {Central Role of Sibling Small RNAs NgncR_162 and NgncR_163 in Main Metabolic Pathways of Neisseria gonorrhoeae}, series = {mBio}, volume = {14}, journal = {mBio}, doi = {10.1128/mbio.03093-22}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313323}, year = {2023}, abstract = {Small bacterial regulatory RNAs (sRNAs) have been implicated in the regulation of numerous metabolic pathways. In most of these studies, sRNA-dependent regulation of mRNAs or proteins of enzymes in metabolic pathways has been predicted to affect the metabolism of these bacteria. However, only in a very few cases has the role in metabolism been demonstrated. Here, we performed a combined transcriptome and metabolome analysis to define the regulon of the sibling sRNAs NgncR_162 and NgncR_163 (NgncR_162/163) and their impact on the metabolism of Neisseria gonorrhoeae. These sRNAs have been reported to control genes of the citric acid and methylcitric acid cycles by posttranscriptional negative regulation. By transcriptome analysis, we now expand the NgncR_162/163 regulon by several new members and provide evidence that the sibling sRNAs act as both negative and positive regulators of target gene expression. Newly identified NgncR_162/163 targets are mostly involved in transport processes, especially in the uptake of glycine, phenylalanine, and branched-chain amino acids. NgncR_162/163 also play key roles in the control of serine-glycine metabolism and, hence, probably affect biosyntheses of nucleotides, vitamins, and other amino acids via the supply of one-carbon (C\(_1\)) units. Indeed, these roles were confirmed by metabolomics and metabolic flux analysis, which revealed a bipartite metabolic network with glucose degradation for the supply of anabolic pathways and the usage of amino acids via the citric acid cycle for energy metabolism. Thus, by combined deep RNA sequencing (RNA-seq) and metabolomics, we significantly extended the regulon of NgncR_162/163 and demonstrated the role of NgncR_162/163 in the regulation of central metabolic pathways of the gonococcus.}, language = {en} } @article{LibandaPaeth2023, author = {Libanda, Brigadier and Paeth, Heiko}, title = {Modelling wind speed across Zambia: Implications for wind energy}, series = {International Journal of Climatology}, volume = {43}, journal = {International Journal of Climatology}, number = {2}, doi = {10.1002/joc.7826}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312134}, pages = {772 -- 786}, year = {2023}, abstract = {Wind energy is a key option in global dialogues about climate change mitigation. Here, we combined observations from surface wind stations, reanalysis datasets, and state-of-the-art regional climate models from the Coordinated Regional Climate Downscaling Experiment (CORDEX Africa) to study the current and future wind energy potential in Zambia. We found that winds are dominated by southeasterlies and are rarely strong with an average speed of 2.8 m·s\(^{-1}\). When we converted the observed surface wind speed to a turbine hub height of 100 m, we found a ~38\% increase in mean wind speed for the period 1981-2000. Further, both simulated and observed wind speed data show statistically significant increments across much of the country. The only areas that divert from this upward trend of wind speeds are the low land terrains of the Eastern Province bordering Malawi. Examining projections of wind power density (WPD), we found that although wind speed is increasing, it is still generally too weak to support large-scale wind power generation. We found a meagre projected annual average WPD of 46.6 W·m\(^{-2}\). The highest WPDs of ~80 W·m\(^{-2}\) are projected in the northern and central parts of the country while the lowest are to be expected along the Luangwa valley in agreement with wind speed simulations. On average, Zambia is expected to experience minor WPD increments of 0.004 W·m\(^{-2}\) per year from 2031 to 2050. We conclude that small-scale wind turbines that accommodate cut-in wind speeds of 3.8 m·s\(^{-1}\) are the most suitable for power generation in Zambia. Further, given the limitations of small wind turbines, they are best suited for rural and suburban areas of the country where obstructions are few, thus making them ideal for complementing the government of the Republic of Zambia's rural electrification efforts.}, language = {en} } @article{LambergerZainuddinScheibeletal.2023, author = {Lamberger, Zan and Zainuddin, Shakir and Scheibel, Thomas and Lang, Gregor}, title = {Polymeric Janus Fibers}, series = {ChemPlusChem}, volume = {88}, journal = {ChemPlusChem}, number = {2}, doi = {10.1002/cplu.202200371}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318516}, year = {2023}, abstract = {Janus fibers are a class of composite materials comprising mechanical and chemical to biological functionality. Combining different materials and functionalities in one micro- or even nanoscale fiber enables otherwise unreachable synergistic physicochemical effects with unprecedented opportunities for technical or biomedical applications. Here, recent developments of processing technologies and applications of polymeric Janus fibers will be reviewed. Various examples in the fields of textiles, catalysis, sensors as well as medical applications, like drug delivery systems, tissue engineering and antimicrobial materials, are presented to illuminate the outstanding potential of such high-end functional materials for novel applications in the upcoming future.}, language = {en} } @article{DhillonDahmsKuebertFlocketal.2023, author = {Dhillon, Maninder Singh and Dahms, Thorsten and Kuebert-Flock, Carina and Rummler, Thomas and Arnault, Joel and Steffan-Dewenter, Ingolf and Ullmann, Tobias}, title = {Integrating random forest and crop modeling improves the crop yield prediction of winter wheat and oil seed rape}, series = {Frontiers in Remote Sensing}, volume = {3}, journal = {Frontiers in Remote Sensing}, issn = {2673-6187}, doi = {10.3389/frsen.2022.1010978}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301462}, year = {2023}, abstract = {The fast and accurate yield estimates with the increasing availability and variety of global satellite products and the rapid development of new algorithms remain a goal for precision agriculture and food security. However, the consistency and reliability of suitable methodologies that provide accurate crop yield outcomes still need to be explored. The study investigates the coupling of crop modeling and machine learning (ML) to improve the yield prediction of winter wheat (WW) and oil seed rape (OSR) and provides examples for the Free State of Bavaria (70,550 km2), Germany, in 2019. The main objectives are to find whether a coupling approach [Light Use Efficiency (LUE) + Random Forest (RF)] would result in better and more accurate yield predictions compared to results provided with other models not using the LUE. Four different RF models [RF1 (input: Normalized Difference Vegetation Index (NDVI)), RF2 (input: climate variables), RF3 (input: NDVI + climate variables), RF4 (input: LUE generated biomass + climate variables)], and one semi-empiric LUE model were designed with different input requirements to find the best predictors of crop monitoring. The results indicate that the individual use of the NDVI (in RF1) and the climate variables (in RF2) could not be the most accurate, reliable, and precise solution for crop monitoring; however, their combined use (in RF3) resulted in higher accuracies. Notably, the study suggested the coupling of the LUE model variables to the RF4 model can reduce the relative root mean square error (RRMSE) from -8\% (WW) and -1.6\% (OSR) and increase the R 2 by 14.3\% (for both WW and OSR), compared to results just relying on LUE. Moreover, the research compares models yield outputs by inputting three different spatial inputs: Sentinel-2(S)-MOD13Q1 (10 m), Landsat (L)-MOD13Q1 (30 m), and MOD13Q1 (MODIS) (250 m). The S-MOD13Q1 data has relatively improved the performance of models with higher mean R 2 [0.80 (WW), 0.69 (OSR)], and lower RRMSE (\%) (9.18, 10.21) compared to L-MOD13Q1 (30 m) and MOD13Q1 (250 m). Satellite-based crop biomass, solar radiation, and temperature are found to be the most influential variables in the yield prediction of both crops.}, language = {en} } @article{Ibebuchi2023, author = {Ibebuchi, Chibuike Chiedozie}, title = {On the representation of atmospheric circulation modes in regional climate models over Western Europe}, series = {International Journal of Climatology}, volume = {43}, journal = {International Journal of Climatology}, number = {1}, doi = {10.1002/joc.7807}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312424}, pages = {668 -- 682}, year = {2023}, abstract = {Atmospheric circulation is a key driver of climate variability, and the representation of atmospheric circulation modes in regional climate models (RCMs) can enhance the credibility of regional climate projections. This study examines the representation of large-scale atmospheric circulation modes in Coupled Model Inter-comparison Project phase 5 RCMs once driven by ERA-Interim, and by two general circulation models (GCMs). The study region is Western Europe and the circulation modes are classified using the Promax rotated T-mode principal component analysis. The results indicate that the RCMs can replicate the classified atmospheric modes as obtained from ERA5 reanalysis, though with biases dependent on the data providing the lateral boundary condition and the choice of RCM. When the boundary condition is provided by ERA-Interim that is more consistent with observations, the simulated map types and the associating time series match well with their counterparts from ERA5. Further, on average, the multi-model ensemble mean of the analysed RCMs, driven by ERA-Interim, indicated a slight improvement in the representation of the modes obtained from ERA5. Conversely, when the RCMs are driven by the GCMs that are models without assimilation of observational data, the representation of the atmospheric modes, as obtained from ERA5, is relatively less accurate compared to when the RCMs are driven by ERA-Interim. This suggests that the biases stem from the GCMs. On average, the representation of the modes was not improved in the multi-model ensemble mean of the five analysed RCMs driven by either of the GCMs. However, when the best-performed RCMs were selected on average the ensemble mean indicated a slight improvement. Moreover, the presence of the North Atlantic Oscillation (NAO) in the simulated modes depends also on the lateral boundary conditions. The relationship between the modes and the NAO was replicated only when the RCMs were driven by reanalysis. The results indicate that the forcing model is the main factor in reproducing the atmospheric circulation.}, language = {en} } @article{MenekseMahlAlbertetal.2023, author = {Menekse, Kaan and Mahl, Magnus and Albert, Julius and Niyas, M. A. and Shoyama, Kazutaka and Stolte, Matthias and W{\"u}rthner, Frank}, title = {Supramolecularly Engineered Bulk-Heterojunction Solar Cells with Self-Assembled Non-Fullerene Nanographene Tetraimide Acceptors}, series = {Solar RRL}, volume = {7}, journal = {Solar RRL}, number = {2}, doi = {10.1002/solr.202200895}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312099}, year = {2023}, abstract = {A series of novel imide-functionalized C\(_{64}\) nanographenes is investigated as acceptor components in organic solar cells (OSCs) in combination with donor polymer PM6. These electron-poor molecules either prevail as a monomer or self-assemble into dimers in the OSC active layer depending on the chosen imide substituents. This allows for the controlled stacking of electron-poor and electron-rich π-scaffolds to establish a novel class of non-fullerene acceptor materials to tailor the bulk-heterojunction morphology of the OSCs. The best performance is observed for derivatives that are able to self-assemble into dimers, reaching power conversion efficiencies of up to 7.1\%.}, language = {en} } @article{MaihoffFriessHoissetal.2023, author = {Maihoff, Fabienne and Friess, Nicolas and Hoiss, Bernhard and Schmid-Egger, Christian and Kerner, Janika and Neumayer, Johann and Hopfenm{\"u}ller, Sebastian and B{\"a}ssler, Claus and M{\"u}ller, J{\"o}rg and Classen, Alice}, title = {Smaller, more diverse and on the way to the top: Rapid community shifts of montane wild bees within an extraordinary hot decade}, series = {Diversity and Distributions}, volume = {29}, journal = {Diversity and Distributions}, number = {2}, doi = {10.1111/ddi.13658}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312126}, pages = {272-288}, year = {2023}, abstract = {Aim Global warming is assumed to restructure mountain insect communities in space and time. Theory and observations along climate gradients predict that insect abundance and richness, especially of small-bodied species, will increase with increasing temperature. However, the specific responses of single species to rising temperatures, such as spatial range shifts, also alter communities, calling for intensive monitoring of real-world communities over time. Location German Alps and pre-alpine forests in south-east Germany. Methods We empirically examined the temporal and spatial change in wild bee communities and its drivers along two largely well-protected elevational gradients (alpine grassland vs. pre-alpine forest), each sampled twice within the last decade. Results We detected clear abundance-based upward shifts in bee communities, particularly in cold-adapted bumble bee species, demonstrating the speed with which mobile organisms can respond to climatic changes. Mean annual temperature was identified as the main driver of species richness in both regions. Accordingly, and in large overlap with expectations under climate warming, we detected an increase in bee richness and abundance, and an increase in small-bodied species in low- and mid-elevations along the grassland gradient. Community responses in the pre-alpine forest gradient were only partly consistent with community responses in alpine grasslands. Main Conclusion In well-protected temperate mountain regions, small-bodied bees may initially profit from warming temperatures, by getting more abundant and diverse. Less severe warming, and differences in habitat openness along the forested gradient, however, might moderate species responses. Our study further highlights the utility of standardized abundance data for revealing rapid changes in bee communities over only one decade.}, language = {en} } @article{DeğirmenciRogeFerreiraVukosavljevicetal.2023, author = {Değirmenci, Laura and Rog{\´e} Ferreira, Fabio Luiz and Vukosavljevic, Adrian and Heindl, Cornelia and Keller, Alexander and Geiger, Dietmar and Scheiner, Ricarda}, title = {Sugar perception in honeybees}, series = {Frontiers in Physiology}, volume = {13}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2022.1089669}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-302284}, year = {2023}, abstract = {Honeybees (Apis mellifera) need their fine sense of taste to evaluate nectar and pollen sources. Gustatory receptors (Grs) translate taste signals into electrical responses. In vivo experiments have demonstrated collective responses of the whole Gr-set. We here disentangle the contributions of all three honeybee sugar receptors (AmGr1-3), combining CRISPR/Cas9 mediated genetic knock-out, electrophysiology and behaviour. We show an expanded sugar spectrum of the AmGr1 receptor. Mutants lacking AmGr1 have a reduced response to sucrose and glucose but not to fructose. AmGr2 solely acts as co-receptor of AmGr1 but not of AmGr3, as we show by electrophysiology and using bimolecular fluorescence complementation. Our results show for the first time that AmGr2 is indeed a functional receptor on its own. Intriguingly, AmGr2 mutants still display a wildtype-like sugar taste. AmGr3 is a specific fructose receptor and is not modulated by a co-receptor. Eliminating AmGr3 while preserving AmGr1 and AmGr2 abolishes the perception of fructose but not of sucrose. Our comprehensive study on the functions of AmGr1, AmGr2 and AmGr3 in honeybees is the first to combine investigations on sugar perception at the receptor level and simultaneously in vivo. We show that honeybees rely on two gustatory receptors to sense all relevant sugars.}, language = {en} } @article{HanRenMamtiminetal.2023, author = {Han, Chao and Ren, Pengxuan and Mamtimin, Medina and Kruk, Linus and Sarukhanyan, Edita and Li, Chenyu and Anders, Hans-Joachim and Dandekar, Thomas and Krueger, Irena and Elvers, Margitta and Goebel, Silvia and Adler, Kristin and M{\"u}nch, G{\"o}tz and Gudermann, Thomas and Braun, Attila and Mammadova-Bach, Elmina}, title = {Minimal collagen-binding epitope of glycoprotein VI in human and mouse platelets}, series = {Biomedicines}, volume = {11}, journal = {Biomedicines}, number = {2}, issn = {2227-9059}, doi = {10.3390/biomedicines11020423}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304148}, year = {2023}, abstract = {Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin, regulating important platelet functions such as platelet adhesion and thrombus growth. Although the blockade of GPVI function is widely recognized as a potent anti-thrombotic approach, there are limited studies focused on site-specific targeting of GPVI. Using computational modeling and bioinformatics, we analyzed collagen- and CRP-binding surfaces of GPVI monomers and dimers, and compared the interacting surfaces with other mammalian GPVI isoforms. We could predict a minimal collagen-binding epitope of GPVI dimer and designed an EA-20 antibody that recognizes a linear epitope of this surface. Using platelets and whole blood samples donated from wild-type and humanized GPVI transgenic mice and also humans, our experimental results show that the EA-20 antibody inhibits platelet adhesion and aggregation in response to collagen and CRP, but not to fibrin. The EA-20 antibody also prevents thrombus formation in whole blood, on the collagen-coated surface, in arterial flow conditions. We also show that EA-20 does not influence GPVI clustering or receptor shedding. Therefore, we propose that blockade of this minimal collagen-binding epitope of GPVI with the EA-20 antibody could represent a new anti-thrombotic approach by inhibiting specific interactions between GPVI and the collagen matrix.}, language = {en} } @article{WabnitzSchwienhorstStichAsbecketal.2023, author = {Wabnitz, Katharina and Schwienhorst-Stich, Eva-Maria and Asbeck, Franziska and Fellmann, Cara Sophie and Gepp, Sophie and Leberl, Jana and Mezger, Nikolaus Christian Simon and Eichinger, Michael}, title = {National Planetary Health learning objectives for Germany: A steppingstone for medical education to promote transformative change}, series = {Frontiers in Public Health}, volume = {10}, journal = {Frontiers in Public Health}, issn = {2296-2565}, doi = {10.3389/fpubh.2022.1093720}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-306027}, year = {2023}, abstract = {Physicians play an important role in adapting to and mitigating the adverse health effects of the unfolding climate and ecological crises. To fully harness this potential, future physicians need to acquire knowledge, values, skills, and leadership attributes to care for patients presenting with environmental change-related conditions and to initiate and propel transformative change in healthcare and other sectors of society including, but not limited to, the decarbonization of healthcare systems, the transition to renewable energies and the transformation of transport and food systems. Despite the potential of Planetary Health Education (PHE) to support medical students in becoming agents of change, best-practice examples of mainstreaming PHE in medical curricula remain scarce both in Germany and internationally. The process of revising and updating the Medical Licensing Regulations and the National Competency-based Catalog of Learning Objectives for Medical Education in Germany provided a window of opportunity to address this implementation challenge. In this article, we describe the development and content of national Planetary Health learning objectives for Germany. We anticipate that the learning objectives will stimulate the development and implementation of innovative Planetary Health teaching, learning and exam formats in medical schools and inform similar initiatives in other health professions. The availability of Planetary Health learning objectives in other countries will provide opportunities for cross-country and interdisciplinary exchange of experiences and validation of content, thus supporting the consolidation of Planetary Health learning objectives and the improvement of PHE for all health professionals globally.}, language = {en} } @article{SchmidtZeheHolzgrabe2023, author = {Schmidt, Sebastian and Zehe, Markus and Holzgrabe, Ulrike}, title = {Characterization of binding properties of ephedrine derivatives to human alpha-1-acid glycoprotein}, series = {European Journal of Pharmaceutical Sciences}, volume = {181}, journal = {European Journal of Pharmaceutical Sciences}, doi = {10.1016/j.ejps.2022.106333}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300848}, year = {2023}, abstract = {Most drugs, especially those with acidic or neutral moieties, are bound to the plasma protein albumin, whereas basic drugs are preferentially bound to human alpha-1-acid glycoprotein (AGP). The protein binding of the long-established drugs ephedrine and pseudoephedrine, which are used in the treatment of hypotension and colds, has so far only been studied with albumin. Since in a previous study a stereoselective binding of ephedrine and pseudoephedrine to serum but not to albumin was observed, the aim of this study was to check whether the enantioselective binding behavior of ephedrine and pseudoephedrine, in addition to the derivatives methylephedrine and norephedrine, is due to AGP and to investigate the influence of their different substituents and steric arrangement. Discontinuous ultrafiltration was used for the determination of protein binding. Characterization of ligand-protein interactions of the drugs was obtained by saturation transfer difference nuclear magnetic resonance spectroscopy. Docking experiments were performed to analyze possible ligand-protein interactions. The more basic the ephedrine derivative is, the higher is the affinity to AGP. There was no significant difference in the binding properties between the individual enantiomers and the diastereomers of ephedrine and pseudoephedrine.}, language = {en} } @article{ScheitlOkudaAdelmannetal.2023, author = {Scheitl, Carolin P. M. and Okuda, Takumi and Adelmann, Juliane and H{\"o}bartner, Claudia}, title = {Ribozyme-catalyzed late-stage functionalization and fluorogenic labeling of RNA}, series = {Angewandte Chemie International Edition}, volume = {62}, journal = {Angewandte Chemie International Edition}, doi = {10.1002/anie.202305463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327543}, year = {2023}, abstract = {Site-specific introduction of biorthogonal handles into RNAs is in high demand for decorating RNAs with fluorophores, affinity labels or other modifications. Aldehydes represent attractive functional groups for post-synthetic bioconjugation reactions. Here, we report a ribozyme-based method for the synthesis of aldehyde-functionalized RNA by directly converting a purine nucleobase. Using the methyltransferase ribozyme MTR1 as an alkyltransferase, the reaction is initiated by site-specific N1 benzylation of purine, followed by nucleophilic ring opening and spontaneous hydrolysis under mild conditions to yield a 5-amino-4-formylimidazole residue in good yields. The modified nucleotide is accessible to aldehyde-reactive probes, as demonstrated by the conjugation of biotin or fluorescent dyes to short synthetic RNAs and tRNA transcripts. Upon fluorogenic condensation with a 2,3,3-trimethylindole, a novel hemicyanine chromophore was generated directly on the RNA. This work expands the MTR1 ribozyme's area of application from a methyltransferase to a tool for site-specific late-stage functionalization of RNA.}, language = {en} } @article{BalonovKurlbaumKoschkeretal.2023, author = {Balonov, Ilja and Kurlbaum, Max and Koschker, Ann-Cathrin and Stier, Christine and Fassnacht, Martin and Dischinger, Ulrich}, title = {Changes in plasma metabolomic profile following bariatric surgery, lifestyle intervention or diet restriction — insights from human and rat studies}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {3}, issn = {1422-0067}, doi = {10.3390/ijms24032354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304462}, year = {2023}, abstract = {Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans, translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled W{\"u}rzburg Adipositas Study (WAS) and from RYGB-treated rats (n = 6) as well as body-weight-matched controls (n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI -34.3\% (OP) vs. -1.2\% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss.}, language = {en} } @article{MrestaniLichterSirenetal.2023, author = {Mrestani, Achmed and Lichter, Katharina and Sir{\´e}n, Anna-Leena and Heckmann, Manfred and Paul, Mila M. and Pauli, Martin}, title = {Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {3}, issn = {1422-0067}, doi = {10.3390/ijms24032128}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304904}, year = {2023}, abstract = {Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22\% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations.}, language = {en} } @article{OuedraogoHackmanThieletal.2023, author = {Ouedraogo, Valentin and Hackman, Kwame Oppong and Thiel, Michael and Dukiya, Jaiye}, title = {Intensity analysis for urban Land Use/Land Cover dynamics characterization of Ouagadougou and Bobo-Dioulasso in Burkina Faso}, series = {Land}, volume = {12}, journal = {Land}, number = {5}, issn = {2073-445X}, doi = {10.3390/land12051063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319397}, year = {2023}, abstract = {Ouagadougou and Bobo-Dioulasso remain the two major urban centers in Burkina Faso with an increasing trend in human footprint. The research aimed at analyzing the Land Use/Land Cover (LULC) dynamics in the two cities between 2003 and 2021 using intensity analysis, which decomposes LULC changes into interval, category and transition levels. The satellite data used for this research were composed of surface reflectance imagery from Landsat 5, Landsat 7 and Landsat 8 acquired from the Google Earth Engine Data Catalogue. The Random Forest, Support Vector Machine and Gradient Tree Boost algorithms were employed to run supervised image classifications for four selected years including 2003, 2009, 2015 and 2021. The results showed that the landscape is changing in both cities due to rapid urbanization. Ouagadougou experienced more rapid changes than Bobo-Dioulasso, with a maximum annual change intensity of 3.61\% recorded between 2015 and 2021 against 2.22\% in Bobo-Dioulasso for the period 2009-2015. The transition of change was mainly towards built-up areas, which gain targeted bare and agricultural lands in both cities. This situation has led to a 78.12\% increase of built-up surfaces in Ouagadougou, while 42.24\% of agricultural land area was lost. However, in Bobo-Dioulasso, the built class has increased far more by 140.67\%, and the agricultural land areas experienced a gain of 1.38\% compared with the 2003 baseline. The study demonstrates that the human footprint is increasing in both cities making the inhabitants vulnerable to environmental threats such as flooding and the effect of an Urban Heat Island, which is information that could serve as guide for sustainable urban land use planning.}, language = {en} } @article{MuellerMetaMeidneretal.2023, author = {M{\"u}ller, Patrick and Meta, Mergim and Meidner, Jan Laurenz and Schwickert, Marvin and Meyr, Jessica and Schwickert, Kevin and Kersten, Christian and Zimmer, Collin and Hammerschmidt, Stefan Josef and Frey, Ariane and Lahu, Albin and de la Hoz-Rodr{\´i}guez, Sergio and Agost-Beltr{\´a}n, Laura and Rodr{\´i}guez, Santiago and Diemer, Kira and Neumann, Wilhelm and Gonz{\`a}lez, Florenci V. and Engels, Bernd and Schirmeister, Tanja}, title = {Investigation of the compatibility between warheads and peptidomimetic sequences of protease inhibitors — a comprehensive reactivity and selectivity study}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {8}, issn = {1422-0067}, doi = {10.3390/ijms24087226}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313596}, year = {2023}, abstract = {Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding. Therefore, the right combination of a reactive warhead with a well-suited peptidomimetic sequence is of great importance. Herein, the selectivities of well-known warheads combined with peptidomimetic sequences suited for five different proteases were investigated, highlighting the impact of both structure parts (warhead and peptidomimetic sequence) for affinity and selectivity. Molecular docking gave insights into the predicted binding modes of the inhibitors inside the binding pockets of the different enzymes. Moreover, the warheads were investigated by NMR and LC-MS reactivity assays against serine/threonine and cysteine nucleophile models, as well as by quantum mechanics simulations.}, language = {en} } @article{FeiglStahringerPeindletal.2023, author = {Feigl, Frederik Fabian and Stahringer, Anika and Peindl, Matthias and Dandekar, Gudrun and Koehl, Ulrike and Fricke, Stephan and Schmiedel, Dominik}, title = {Efficient redirection of NK cells by genetic modification with chemokine receptors CCR4 and CCR2B}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {4}, issn = {1422-0067}, doi = {10.3390/ijms24043129}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304049}, year = {2023}, abstract = {Natural killer (NK) cells are a subset of lymphocytes that offer great potential for cancer immunotherapy due to their natural anti-tumor activity and the possibility to safely transplant cells from healthy donors to patients in a clinical setting. However, the efficacy of cell-based immunotherapies using both T and NK cells is often limited by a poor infiltration of immune cells into solid tumors. Importantly, regulatory immune cell subsets are frequently recruited to tumor sites. In this study, we overexpressed two chemokine receptors, CCR4 and CCR2B, that are naturally found on T regulatory cells and tumor-resident monocytes, respectively, on NK cells. Using the NK cell line NK-92 as well as primary NK cells from peripheral blood, we show that genetically engineered NK cells can be efficiently redirected using chemokine receptors from different immune cell lineages and migrate towards chemokines such as CCL22 or CCL2, without impairing the natural effector functions. This approach has the potential to enhance the therapeutic effect of immunotherapies in solid tumors by directing genetically engineered donor NK cells to tumor sites. As a future therapeutic option, the natural anti-tumor activity of NK cells at the tumor sites can be increased by co-expression of chemokine receptors with chimeric antigen receptors (CAR) or T cell receptors (TCR) on NK cells can be performed in the future.}, language = {en} } @article{GoeritzerKuentzelBecketal.2023, author = {Goeritzer, Madeleine and Kuentzel, Katharina B. and Beck, Sarah and Korbelius, Melanie and Rainer, Silvia and Bradić, Ivan and Kolb, Dagmar and Mussbacher, Marion and Schrottmaier, Waltraud C. and Assinger, Alice and Schlagenhauf, Axel and Rost, Ren{\´e} and Gottschalk, Benjamin and Eichmann, Thomas O. and Z{\"u}llig, Thomas and Graier, Wolfgang F. and Vujić, Nemanja and Kratky, Dagmar}, title = {Monoglyceride lipase deficiency is associated with altered thrombogenesis in mice}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {4}, issn = {1422-0067}, doi = {10.3390/ijms24043116}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304052}, year = {2023}, abstract = {Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) to glycerol and one fatty acid. Among the various MG species, MGL also degrades 2-arachidonoylglycerol, the most abundant endocannabinoid and potent activator of the cannabinoid receptors 1 and 2. We investigated the consequences of MGL deficiency on platelet function using systemic (Mgl\(^{-/-}\)) and platelet-specific Mgl-deficient (platMgl\(^{-/-}\)) mice. Despite comparable platelet morphology, loss of MGL was associated with decreased platelet aggregation and reduced response to collagen activation. This was reflected by reduced thrombus formation in vitro, accompanied by a longer bleeding time and a higher blood volume loss. Occlusion time after FeCl\(_3\)-induced injury was markedly reduced in Mgl\(^{-/-}\) mice, which is consistent with contraction of large aggregates and fewer small aggregates in vitro. The absence of any functional changes in platelets from platMgl\(^{-/-}\) mice is in accordance with lipid degradation products or other molecules in the circulation, rather than platelet-specific effects, being responsible for the observed alterations in Mgl\(^{-/-}\) mice. We conclude that genetic deletion of MGL is associated with altered thrombogenesis.}, language = {en} } @article{SolimandoBittrichShahinietal.2023, author = {Solimando, Antonio G. and Bittrich, Max and Shahini, Endrit and Albanese, Federica and Fritz, Georg and Krebs, Markus}, title = {Determinants of COVID-19 disease severity - lessons from primary and secondary immune disorders including cancer}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {10}, issn = {1422-0067}, doi = {10.3390/ijms24108746}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319412}, year = {2023}, abstract = {At the beginning of the COVID-19 pandemic, patients with primary and secondary immune disorders — including patients suffering from cancer — were generally regarded as a high-risk population in terms of COVID-19 disease severity and mortality. By now, scientific evidence indicates that there is substantial heterogeneity regarding the vulnerability towards COVID-19 in patients with immune disorders. In this review, we aimed to summarize the current knowledge about the effect of coexistent immune disorders on COVID-19 disease severity and vaccination response. In this context, we also regarded cancer as a secondary immune disorder. While patients with hematological malignancies displayed lower seroconversion rates after vaccination in some studies, a majority of cancer patients' risk factors for severe COVID-19 disease were either inherent (such as metastatic or progressive disease) or comparable to the general population (age, male gender and comorbidities such as kidney or liver disease). A deeper understanding is needed to better define patient subgroups at a higher risk for severe COVID-19 disease courses. At the same time, immune disorders as functional disease models offer further insights into the role of specific immune cells and cytokines when orchestrating the immune response towards SARS-CoV-2 infection. Longitudinal serological studies are urgently needed to determine the extent and the duration of SARS-CoV-2 immunity in the general population, as well as immune-compromised and oncological patients.}, language = {en} } @article{PagottoSimeoneBroccoetal.2023, author = {Pagotto, Sara and Simeone, Pasquale and Brocco, Davide and Catitti, Giulia and De Bellis, Domenico and Vespa, Simone and Di Pietro, Natalia and Marinelli, Lisa and Di Stefano, Antonio and Veschi, Serena and De Lellis, Laura and Verginelli, Fabio and Kaitsas, Francesco and Iezzi, Manuela and Pandolfi, Assunta and Visone, Rosa and Tinari, Nicola and Caruana, Ignazio and Di Ianni, Mauro and Cama, Alessandro and Lanuti, Paola and Florio, Rosalba}, title = {CAR-T-derived extracellular vesicles: a promising development of CAR-T anti-tumor therapy}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {4}, issn = {2072-6694}, doi = {10.3390/cancers15041052}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304195}, year = {2023}, abstract = {Extracellular vesicles (EVs) are a heterogenous population of plasma membrane-surrounded particles that are released in the extracellular milieu by almost all types of living cells. EVs are key players in intercellular crosstalk, both locally and systemically, given that they deliver their cargoes (consisting of proteins, lipids, mRNAs, miRNAs, and DNA fragments) to target cells, crossing biological barriers. Those mechanisms further trigger a wide range of biological responses. Interestingly, EV phenotypes and cargoes and, therefore, their functions, stem from their specific parental cells. For these reasons, EVs have been proposed as promising candidates for EV-based, cell-free therapies. One of the new frontiers of cell-based immunotherapy for the fight against refractory neoplastic diseases is represented by genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes, which in recent years have demonstrated their effectiveness by reaching commercialization and clinical application for some neoplastic diseases. CAR-T-derived EVs represent a recent promising development of CAR-T immunotherapy approaches. This crosscutting innovative strategy is designed to exploit the advantages of genetically engineered cell-based immunotherapy together with those of cell-free EVs, which in principle might be safer and more efficient in crossing biological and tumor-associated barriers. In this review, we underlined the potential of CAR-T-derived EVs as therapeutic agents in tumors.}, language = {en} } @article{VergoteMacarullaHirschetal.2023, author = {Vergote, Ignace and Macarulla, Teresa and Hirsch, Fred R. and Hagemann, Carsten and Miller, David Scott}, title = {Tumor Treating Fields (TTFields) therapy concomitant with taxanes for cancer treatment}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {3}, issn = {2072-6694}, doi = {10.3390/cancers15030636}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305007}, year = {2023}, abstract = {Non-small cell lung cancer, ovarian cancer, and pancreatic cancer all present with high morbidity and mortality. Systemic chemotherapies have historically been the cornerstone of standard of care (SOC) regimens for many cancers, but are associated with systemic toxicity. Multimodal treatment combinations can help improve patient outcomes; however, implementation is limited by additive toxicities and potential drug-drug interactions. As such, there is a high unmet need to develop additional therapies to enhance the efficacy of SOC treatments without increasing toxicity. Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. The therapy is locoregional and is delivered noninvasively to the tumor site via a portable medical device that consists of field generator and arrays that are placed on the patient's skin. As a noninvasive treatment modality, TTFields therapy-related adverse events mainly consist of localized skin reactions, which are manageable with effective acute and prophylactic treatments. TTFields selectively target cancer cells through a multi-mechanistic approach without affecting healthy cells and tissues. Therefore, the application of TTFields therapy concomitant with other cancer treatments may lead to enhanced efficacy, with low risk of further systemic toxicity. In this review, we explore TTFields therapy concomitant with taxanes in both preclinical and clinical settings. The summarized data suggest that TTFields therapy concomitant with taxanes may be beneficial in the treatment of certain cancers.}, language = {en} } @article{LuuSchuetzLauthetal.2023, author = {Luu, Maik and Sch{\"u}tz, Burkhard and Lauth, Matthias and Visekruna, Alexander}, title = {The impact of gut microbiota-derived metabolites on the tumor immune microenvironment}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {5}, issn = {2072-6694}, doi = {10.3390/cancers15051588}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311005}, year = {2023}, abstract = {Prevention of the effectiveness of anti-tumor immune responses is one of the canonical cancer hallmarks. The competition for crucial nutrients within the tumor microenvironment (TME) between cancer cells and immune cells creates a complex interplay characterized by metabolic deprivation. Extensive efforts have recently been made to understand better the dynamic interactions between cancer cells and surrounding immune cells. Paradoxically, both cancer cells and activated T cells are metabolically dependent on glycolysis, even in the presence of oxygen, a metabolic process known as the Warburg effect. The intestinal microbial community delivers various types of small molecules that can potentially augment the functional capabilities of the host immune system. Currently, several studies are trying to explore the complex functional relationship between the metabolites secreted by the human microbiome and anti-tumor immunity. Recently, it has been shown that a diverse array of commensal bacteria synthetizes bioactive molecules that enhance the efficacy of cancer immunotherapy, including immune checkpoint inhibitor (ICI) treatment and adoptive cell therapy with chimeric antigen receptor (CAR) T cells. In this review, we highlight the importance of commensal bacteria, particularly of the gut microbiota-derived metabolites that are capable of shaping metabolic, transcriptional and epigenetic processes within the TME in a therapeutically meaningful way.}, language = {en} } @article{WobserGoebeler2023, author = {Wobser, Marion and Goebeler, Matthias}, title = {Special Issue "Cutaneous Lymphomas"}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {5}, issn = {2072-6694}, doi = {10.3390/cancers15051481}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304180}, year = {2023}, abstract = {No abstract available}, language = {en} } @article{JedeHenzeMeinersetal.2023, author = {Jede, Christian and Henze, Laura J. and Meiners, Kirstin and Bogdahn, Malte and Wedel, Marcel and van Axel, Valeria}, title = {Development and application of a dissolution-transfer-partitioning system (DTPS) for biopharmaceutical drug characterization}, series = {Pharmaceutics}, volume = {15}, journal = {Pharmaceutics}, number = {4}, issn = {1999-4923}, doi = {10.3390/pharmaceutics15041069}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311149}, year = {2023}, abstract = {A variety of in vitro dissolution and gastrointestinal transfer models have been developed aiming to predict drug supersaturation and precipitation. Further, biphasic, one-vessel in vitro systems are increasingly applied to simulate drug absorption in vitro. However, to date, there is a lack of combining the two approaches. Therefore, the first aim of this study was to develop a dissolution-transfer-partitioning system (DTPS) and, secondly, to assess its biopredictive power. In the DTPS, simulated gastric and intestinal dissolution vessels are connected via a peristaltic pump. An organic layer is added on top of the intestinal phase, serving as an absorptive compartment. The predictive power of the novel DTPS was assessed to a classical USP II transfer model using a BCS class II weak base with poor aqueous solubility, MSC-A. The classical USP II transfer model overestimated simulated intestinal drug precipitation, especially at higher doses. By applying the DTPS, a clearly improved estimation of drug supersaturation and precipitation and an accurate prediction of the in vivo dose linearity of MSC-A were observed. The DTPS provides a useful tool taking both dissolution and absorption into account. This advanced in vitro tool offers the advantage of streamlining the development process of challenging compounds.}, language = {en} } @article{HoubenCelikdemirKervarrecetal.2023, author = {Houben, Roland and Celikdemir, B{\"u}ke and Kervarrec, Thibault and Schrama, David}, title = {Merkel cell polyomavirus: infection, genome, transcripts and its role in development of Merkel cell carcinoma}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers15020444}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305021}, year = {2023}, abstract = {The best characterized polyomavirus family member, i.e., simian virus 40 (SV40), can cause different tumors in hamsters and can transform murine and human cells in vitro. Hence, the SV40 contamination of millions of polio vaccine doses administered from 1955-1963 raised fears that this may cause increased tumor incidence in the vaccinated population. This is, however, not the case. Indeed, up to now, the only polyomavirus family member known to be the most important cause of a specific human tumor entity is Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma (MCC). MCC is a highly deadly form of skin cancer for which the cellular origin is still uncertain, and which appears as two clinically very similar but molecularly highly different variants. While approximately 80\% of cases are found to be associated with MCPyV the remaining MCCs carry a high mutational load. Here, we present an overview of the multitude of molecular functions described for the MCPyV encoded oncoproteins and non-coding RNAs, present the available MCC mouse models and discuss the increasing evidence that both, virus-negative and -positive MCC constitute epithelial tumors.}, language = {en} } @article{KaemmererTribiusCohrsetal.2023, author = {K{\"a}mmerer, Peer W. and Tribius, Silke and Cohrs, Lena and Engler, Gabriel and Ettl, Tobias and Freier, Kolja and Frerich, Bernhard and Ghanaati, Shahram and Gosau, Martin and Haim, Dominik and Hartmann, Stefan and Heiland, Max and Herbst, Manuel and Hoefert, Sebastian and Hoffmann, J{\"u}rgen and H{\"o}lzle, Frank and Howaldt, Hans-Peter and Kreutzer, Kilian and Leonhardt, Henry and Lutz, Rainer and Moergel, Maximilian and Modabber, Ali and Neff, Andreas and Pietzka, Sebastian and Rau, Andrea and Reichert, Torsten E. and Smeets, Ralf and Sproll, Christoph and Steller, Daniel and Wiltfang, J{\"o}rg and Wolff, Klaus-Dietrich and Kronfeld, Kai and Al-Nawas, Bilal}, title = {Adjuvant radiotherapy in patients with squamous cell carcinoma of the oral cavity or oropharynx and solitary ipsilateral lymph node metastasis (pN1) — a prospective multicentric cohort study}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {6}, issn = {2072-6694}, doi = {10.3390/cancers15061833}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311024}, year = {2023}, abstract = {(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.}, language = {en} } @article{KotlyarKrebsSolimandoetal.2023, author = {Kotlyar, Mischa J. and Krebs, Markus and Solimando, Antonio Giovanni and Marquardt, Andr{\´e} and Burger, Maximilian and K{\"u}bler, Hubert and Bargou, Ralf and Kneitz, Susanne and Otto, Wolfgang and Breyer, Johannes and Vergho, Daniel C. and Kneitz, Burkhard and Kalogirou, Charis}, title = {Critical evaluation of a microRNA-based risk classifier predicting cancer-specific survival in renal cell carcinoma with tumor thrombus of the inferior vena cava}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {7}, issn = {2072-6694}, doi = {10.3390/cancers15071981}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311040}, year = {2023}, abstract = {(1) Background: Clear cell renal cell carcinoma extending into the inferior vena cava (ccRCC\(^{IVC}\)) represents a clinical high-risk setting. However, there is substantial heterogeneity within this patient subgroup regarding survival outcomes. Previously, members of our group developed a microRNA(miR)-based risk classifier — containing miR-21-5p, miR-126-3p and miR-221-3p expression — which significantly predicted the cancer-specific survival (CSS) of ccRCC\(^{IVC}\) patients. (2) Methods: Examining a single-center cohort of tumor tissue from n = 56 patients with ccRCC\(^{IVC}\), we measured the expression levels of miR-21, miR-126, and miR-221 using qRT-PCR. The prognostic impact of clinicopathological parameters and miR expression were investigated via single-variable and multivariable Cox regression. Referring to the previously established risk classifier, we performed Kaplan-Meier analyses for single miR expression levels and the combined risk classifier. Cut-off values and weights within the risk classifier were taken from the previous study. (3) Results: miR-21 and miR-126 expression were significantly associated with lymphonodal status at the time of surgery, the development of metastasis during follow-up, and cancer-related death. In Kaplan-Meier analyses, miR-21 and miR-126 significantly impacted CSS in our cohort. Moreover, applying the miR-based risk classifier significantly stratified ccRCC\(^{IVC}\) according to CSS. (4) Conclusions: In our retrospective analysis, we successfully validated the miR-based risk classifier within an independent ccRCC\(^{IVC}\) cohort.}, language = {en} } @article{GorlovaSvirinPavlovetal.2023, author = {Gorlova, Anna and Svirin, Evgeniy and Pavlov, Dmitrii and Cespuglio, Raymond and Proshin, Andrey and Schroeter, Careen A. and Lesch, Klaus-Peter and Strekalova, Tatyana}, title = {Understanding the role of oxidative stress, neuroinflammation and abnormal myelination in excessive aggression associated with depression: recent input from mechanistic studies}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {2}, issn = {1422-0067}, doi = {10.3390/ijms24020915}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304917}, year = {2023}, abstract = {Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities are known to contribute significantly to the accompanying functional impairment and the global burden of disease. Progress in the development of targeted treatments of excessive aggression and accompanying symptoms has been limited, and there exists a major unmet need to develop more efficacious treatments for depressed patients. Due to the complex nature and the clinical heterogeneity of MDD and the lack of precise knowledge regarding its pathophysiology, effective management is challenging. Nonetheless, the aetiology and pathophysiology of MDD has been the subject of extensive research and there is a vast body of the latest literature that points to new mechanisms for this disorder. Here, we overview the key mechanisms, which include neuroinflammation, oxidative stress, insulin receptor signalling and abnormal myelination. We discuss the hypotheses that have been proposed to unify these processes, as many of these pathways are integrated for the neurobiology of MDD. We also describe the current translational approaches in modelling depression, including the recent advances in stress models of MDD, and emerging novel therapies, including novel approaches to management of excessive aggression, such as anti-diabetic drugs, antioxidant treatment and herbal compositions.}, language = {en} } @article{GlaserKernSpeeretal.2023, author = {Glaser, Kirsten and Kern, David and Speer, Christian P. and Schlegel, Nicolas and Schwab, Michael and Thome, Ulrich H. and H{\"a}rtel, Christoph and Wright, Clyde J.}, title = {Imbalanced inflammatory responses in preterm and term cord blood monocytes and expansion of the CD14\(^+\)CD16\(^+\) subset upon toll-like receptor stimulation}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {5}, issn = {1422-0067}, doi = {10.3390/ijms24054919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311056}, year = {2023}, abstract = {Developmentally regulated features of innate immunity are thought to place preterm and term infants at risk of infection and inflammation-related morbidity. Underlying mechanisms are incompletely understood. Differences in monocyte function including toll-like receptor (TLR) expression and signaling have been discussed. Some studies point to generally impaired TLR signaling, others to differences in individual pathways. In the present study, we assessed mRNA and protein expression of pro- and anti-inflammatory cytokines in preterm and term cord blood (CB) monocytes compared with adult controls stimulated ex vivo with Pam3CSK4, zymosan, polyinosinic:polycytidylic acid, lipopolysaccharide, flagellin, and CpG oligonucleotide, which activate the TLR1/2, TLR2/6, TLR3, TLR4, TLR5, and TLR9 pathways, respectively. In parallel, frequencies of monocyte subsets, stimulus-driven TLR expression, and phosphorylation of TLR-associated signaling molecules were analyzed. Independent of stimulus, pro-inflammatory responses of term CB monocytes equaled adult controls. The same held true for preterm CB monocytes—except for lower IL-1β levels. In contrast, CB monocytes released lower amounts of anti-inflammatory IL-10 and IL-1ra, resulting in higher ratios of pro-inflammatory to anti-inflammatory cytokines. Phosphorylation of p65, p38, and ERK1/2 correlated with adult controls. However, stimulated CB samples stood out with higher frequencies of intermediate monocytes (CD14\(^+\)CD16\(^+\)). Both pro-inflammatory net effect and expansion of the intermediate subset were most pronounced upon stimulation with Pam3CSK4 (TLR1/2), zymosan (TR2/6), and lipopolysaccharide (TLR4). Our data demonstrate robust pro-inflammatory and yet attenuated anti-inflammatory responses in preterm and term CB monocytes, along with imbalanced cytokine ratios. Intermediate monocytes, a subset ascribed pro-inflammatory features, might participate in this inflammatory state.}, language = {en} } @article{WatermannMeyerWagneretal.2023, author = {Watermann, Christoph and Meyer, Malin Tordis and Wagner, Steffen and Wittekindt, Claus and Klussmann, Jens Peter and Erguen, Sueleyman and Baumgart-Vogt, Eveline and Karnati, Srikanth}, title = {Peroxisomes are highly abundant and heterogeneous in human parotid glands}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {5}, issn = {1422-0067}, doi = {10.3390/ijms24054783}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311079}, year = {2023}, abstract = {The parotid gland is one of the major salivary glands producing a serous secretion, and it plays an essential role in the digestive and immune systems. Knowledge of peroxisomes in the human parotid gland is minimal; furthermore, the peroxisomal compartment and its enzyme composition in the different cell types of the human parotid gland have never been subjected to a detailed investigation. Therefore, we performed a comprehensive analysis of peroxisomes in the human parotid gland's striated duct and acinar cells. We combined biochemical techniques with various light and electron microscopy techniques to determine the localization of parotid secretory proteins and different peroxisomal marker proteins in parotid gland tissue. Moreover, we analyzed the mRNA of numerous gene encoding proteins localized in peroxisomes using real-time quantitative PCR. The results confirm the presence of peroxisomes in all striated duct and acinar cells of the human parotid gland. Immunofluorescence analyses for various peroxisomal proteins showed a higher abundance and more intense staining in striated duct cells compared to acinar cells. Moreover, human parotid glands comprise high quantities of catalase and other antioxidative enzymes in discrete subcellular regions, suggesting their role in protection against oxidative stress. This study provides the first thorough description of parotid peroxisomes in different parotid cell types of healthy human tissue.}, language = {en} } @article{MichalkeVenkataramani2023, author = {Michalke, Bernhard and Venkataramani, Vivek}, title = {Editorial to the special issue "Homeostasis: metals and cellular redox and immunity status"}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {5}, issn = {1422-0067}, doi = {10.3390/ijms24054889}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311061}, year = {2023}, abstract = {No abstract available}, language = {en} } @article{TejeroAlsakkalHennleinetal.2023, author = {Tejero, Rocio and Alsakkal, Mohammad and Hennlein, Luisa and Lopez-Cabello, Ana M. and Jablonka, Sibylle and Tabares, Lucia}, title = {Nifedipine ameliorates cellular differentiation defects of Smn-deficient motor neurons and enhances neuromuscular transmission in SMA mice}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {8}, issn = {1422-0067}, doi = {10.3390/ijms24087648}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313636}, year = {2023}, abstract = {In spinal muscular atrophy (SMA), mutations in or loss of the Survival Motor Neuron 1 (SMN1) gene reduce full-length SMN protein levels, which leads to the degeneration of a percentage of motor neurons. In mouse models of SMA, the development and maintenance of spinal motor neurons and the neuromuscular junction (NMJ) function are altered. Since nifedipine is known to be neuroprotective and increases neurotransmission in nerve terminals, we investigated its effects on cultured spinal cord motor neurons and motor nerve terminals of control and SMA mice. We found that application of nifedipine increased the frequency of spontaneous Ca\(^{2+}\) transients, growth cone size, cluster-like formations of Cav2.2 channels, and it normalized axon extension in SMA neurons in culture. At the NMJ, nifedipine significantly increased evoked and spontaneous release at low-frequency stimulation in both genotypes. High-strength stimulation revealed that nifedipine increased the size of the readily releasable pool (RRP) of vesicles in control but not SMA mice. These findings provide experimental evidence about the ability of nifedipine to prevent the appearance of developmental defects in SMA embryonic motor neurons in culture and reveal to which extent nifedipine could still increase neurotransmission at the NMJ in SMA mice under different functional demands.}, language = {en} } @article{JostKleinBrandetal.2023, author = {Jost, Priska and Klein, Franziska and Brand, Benjamin and Wahl, Vanessa and Wyatt, Amanda and Yildiz, Daniela and Boehm, Ulrich and Niemeyer, Barbara A. and Vaeth, Martin and Alansary, Dalia}, title = {Acute downregulation but not genetic ablation of murine MCU impairs suppressive capacity of regulatory CD4 T cells}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms24097772}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313621}, year = {2023}, abstract = {By virtue of mitochondrial control of energy production, reactive oxygen species (ROS) generation, and maintenance of Ca\(^{2+}\) homeostasis, mitochondria play an essential role in modulating T cell function. The mitochondrial Ca\(^{2+}\) uniporter (MCU) is the pore-forming unit in the main protein complex mediating mitochondrial Ca\(^{2+}\) uptake. Recently, MCU has been shown to modulate Ca\(^{2+}\) signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation and T cell activation. The mechanisms underlying this modulation and whether MCU has additional T cell subpopulation-specific effects remain elusive. However, mice with germline or tissue-specific ablation of Mcu did not show impaired T cell responses in vitro or in vivo, indicating that 'chronic' loss of MCU can be functionally compensated in lymphocytes. The current work aimed to specifically investigate whether and how MCU influences the suppressive potential of regulatory CD4 T cells (Treg). We show that, in contrast to genetic ablation, acute siRNA-mediated downregulation of Mcu in murine Tregs results in a significant reduction both in mitochondrial Ca\(^{2+}\) uptake and in the suppressive capacity of Tregs, while the ratios of Treg subpopulations and the expression of hallmark transcription factors were not affected. These findings suggest that permanent genetic inactivation of MCU may result in compensatory adaptive mechanisms, masking the effects on the suppressive capacity of Tregs.}, language = {en} } @article{BoeckelKarstenGoepeletal.2023, author = {Boeckel, Hannah and Karsten, Christian M. and G{\"o}pel, Wolfgang and Herting, Egbert and Rupp, Jan and H{\"a}rtel, Christoph and Hartz, Annika}, title = {Increased expression of anaphylatoxin C5a-receptor-1 in neutrophils and natural killer cells of preterm infants}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {12}, issn = {1422-0067}, doi = {10.3390/ijms241210321}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321196}, year = {2023}, abstract = {Preterm infants are susceptible to infection and their defense against pathogens relies largely on innate immunity. The role of the complement system for the immunological vulnerability of preterm infants is less understood. Anaphylatoxin C5a and its receptors C5aR1 and -2 are known to be involved in sepsis pathogenesis, with C5aR1 mainly exerting pro-inflammatory effects. Our explorative study aimed to determine age-dependent changes in the expression of C5aR1 and C5aR2 in neonatal immune cell subsets. Via flow cytometry, we analyzed the expression pattern of C5a receptors on immune cells isolated from peripheral blood of preterm infants (n = 32) compared to those of their mothers (n = 25). Term infants and healthy adults served as controls. Preterm infants had a higher intracellular expression of C5aR1 on neutrophils than control individuals. We also found a higher expression of C5aR1 on NK cells, particularly on the cytotoxic CD56\(^{dim}\) subset and the CD56\(^-\) subset. Immune phenotyping of other leukocyte subpopulations revealed no gestational-age-related differences for the expression of and C5aR2. Elevated expression of C5aR1 on neutrophils and NK cells in preterm infants may contribute to the phenomenon of "immunoparalysis" caused by complement activation or to sustained hyper-inflammatory states. Further functional analyses are needed to elucidate the underlying mechanisms.}, language = {en} } @article{SalvadorKoepplHoermannetal.2023, author = {Salvador, Ellaine and K{\"o}ppl, Theresa and H{\"o}rmann, Julia and Sch{\"o}nh{\"a}rl, Sebastian and Bugaeva, Polina and Kessler, Almuth F. and Burek, Malgorzata and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten}, title = {Tumor Treating Fields (TTFields) induce cell junction alterations in a human 3D in vitro model of the blood-brain barrier}, series = {Pharmaceutics}, volume = {15}, journal = {Pharmaceutics}, number = {1}, issn = {1999-4923}, doi = {10.3390/pharmaceutics15010185}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304830}, year = {2023}, abstract = {In a recent study, we showed in an in vitro murine cerebellar microvascular endothelial cell (cerebEND) model as well as in vivo in rats that Tumor-Treating Fields (TTFields) reversibly open the blood-brain barrier (BBB). This process is facilitated by delocalizing tight junction proteins such as claudin-5 from the membrane to the cytoplasm. In investigating the possibility that the same effects could be observed in human-derived cells, a 3D co-culture model of the BBB was established consisting of primary microvascular brain endothelial cells (HBMVEC) and immortalized pericytes, both of human origin. The TTFields at a frequency of 100 kHz administered for 72 h increased the permeability of our human-derived BBB model. The integrity of the BBB had already recovered 48 h post-TTFields, which is earlier than that observed in cerebEND. The data presented herein validate the previously observed effects of TTFields in murine models. Moreover, due to the fact that human cell-based in vitro models more closely resemble patient-derived entities, our findings are highly relevant for pre-clinical studies.}, language = {en} }