TY - JOUR A1 - Trautmann, Axel A1 - Brockow, Knut A1 - Stoevesandt, Johanna T1 - Metamizole‐induced reactions as a paradigm of drug hypersensitivity: Non‐allergic reactions, anaphylaxis, and delayed‐type allergy JF - Clinical & Experimental Allergy KW - agranulocytosis KW - aspirin‐exacerbated respiratory disease KW - drug adverse reaction KW - drug allergy KW - drug hypersensitivity KW - exanthem KW - fixed drug eruption KW - urticaria Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217997 VL - 50 IS - 9 SP - 1103 EP - 1106 ER - TY - JOUR A1 - Grimm, Clemens A1 - Pelz, Jann-Patrick A1 - Schneider, Cornelius A1 - Schäffler, Katrin A1 - Fischer, Utz T1 - Crystal Structure of a Variant PAM2 Motif of LARP4B Bound to the MLLE Domain of PABPC1 JF - Biomolecules N2 - Eukaryotic cells determine the protein output of their genetic program by regulating mRNA transcription, localization, translation and turnover rates. This regulation is accomplished by an ensemble of RNA-binding proteins (RBPs) that bind to any given mRNA, thus forming mRNPs. Poly(A) binding proteins (PABPs) are prominent members of virtually all mRNPs that possess poly(A) tails. They serve as multifunctional scaffolds, allowing the recruitment of diverse factors containing a poly(A)-interacting motif (PAM) into mRNPs. We present the crystal structure of the variant PAM motif (termed PAM2w) in the N-terminal part of the positive translation factor LARP4B, which binds to the MLLE domain of the poly(A) binding protein C1 cytoplasmic 1 (PABPC1). The structural analysis, along with mutational studies in vitro and in vivo, uncovered a new mode of interaction between PAM2 motifs and MLLE domains. KW - PAM2w KW - PAM2 KW - PABC1 KW - MLLE domain KW - PABP KW - Poly(A) binding protein Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207800 SN - 2218-273X VL - 10 IS - 6 ER - TY - JOUR A1 - Classen, Alice A1 - Eardley, Connal D. A1 - Hemp, Andreas A1 - Peters, Marcell K. A1 - Peters, Ralph S. A1 - Ssymank, Axel A1 - Steffan-Dewenter, Ingolf T1 - Specialization of plant-pollinator interactions increases with temperature at Mt. Kilimanjaro JF - Ecology and Evolution N2 - Aim: Species differ in their degree of specialization when interacting with other species, with significant consequences for the function and robustness of ecosystems. In order to better estimate such consequences, we need to improve our understanding of the spatial patterns and drivers of specialization in interaction networks. Methods: Here, we used the extensive environmental gradient of Mt. Kilimanjaro (Tanzania, East Africa) to study patterns and drivers of specialization, and robustness of plant–pollinator interactions against simulated species extinction with standardized sampling methods. We studied specialization, network robustness and other network indices of 67 quantitative plant–pollinator networks consisting of 268 observational hours and 4,380 plant–pollinator interactions along a 3.4 km elevational gradient. Using path analysis, we tested whether resource availability, pollinator richness, visitation rates, temperature, and/or area explain average specialization in pollinator communities. We further linked pollinator specialization to different pollinator taxa, and species traits, that is, proboscis length, body size, and species elevational ranges. Results: We found that specialization decreased with increasing elevation at different levels of biological organization. Among all variables, mean annual temperature was the best predictor of average specialization in pollinator communities. Specialization differed between pollinator taxa, but was not related to pollinator traits. Network robustness against simulated species extinctions of both plants and pollinators was lowest in the most specialized interaction networks, that is, in the lowlands. Conclusions: Our study uncovers patterns in plant–pollinator specialization along elevational gradients. Mean annual temperature was closely linked to pollinator specialization. Energetic constraints, caused by short activity timeframes in cold highlands, may force ectothermic species to broaden their dietary spectrum. Alternatively or in addition, accelerated evolutionary rates might facilitate the establishment of specialization under warm climates. Despite the mechanisms behind the patterns have yet to be fully resolved, our data suggest that temperature shifts in the course of climate change may destabilize pollination networks by affecting network architecture. KW - altitudinal gradient KW - climate change KW - ecological network KW - functional traits KW - generalization KW - mutualistic interactions KW - network specialization index (H2′) KW - pollination KW - robustness KW - specialization Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235959 VL - 10 IS - 4 ER - TY - JOUR A1 - Wanner, Christoph A1 - Feldt-Rasmussen, Ulla A1 - Jovanovic, Ana A1 - Linhart, Aleš A1 - Yang, Meng A1 - Ponce, Elvira A1 - Brand, Eva A1 - Germain, Dominique P. A1 - Hughes, Derralynn A. A1 - Jefferies, John L. A1 - Martins, Anna Maria A1 - Nowak, Albina A1 - Vujkovac, Bojan A1 - Weidemann, Frank A1 - West, Michael L. A1 - Ortiz, Alberto T1 - Cardiomyopathy and kidney function in agalsidase beta-treated female Fabry patients: a pre-treatment vs. post-treatment analysis JF - ESC Heart Failure N2 - Long-term treatment effect studies in large female Fabry patient groups are challenging to design because of phenotype heterogeneity and lack of appropriate comparison groups, and have not been reported. We compared long-term cardiomyopathy and kidney function outcomes after agalsidase beta treatment with preceding treatment-naive outcomes. Methods and results Self-controlled pretreatment and post-treatment comparison (piecewise mixed linear modelling) included Fabry female patients ≥18 years at treatment initiation who received agalsidase beta (0.9–1.1 mg/kg every other week) for ≥2 years, with ≥2 pretreatment and ≥2 post-treatment outcome measurements during 10-year follow-up. Left ventricular posterior wall thickness (LVPWT)/interventricular septal thickness (IVST) and estimated glomerular filtration rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration creatinine equation) analyses included 42 and 86 patients, respectively, aged 50.0 and 46.3 years at treatment initiation, respectively. LVPWT and IVST increased pretreatment (follow-up 3.5 years) but stabilized during 3.6 years of treatment (LVPWT: n = 38, slope difference [95% confidence interval (CI)] = - 0.41 [ - 0.68, - 0.15] mm/year, P\(_{pre–post difference}\)<0.01; IVST: n = 38, slope difference =-0.32 [-0.67, 0.02] mm/year, P\(_{pre–post difference}\) = 0.07). These findings were not modified by renal involvement or antiproteinuric agent use. Compared with the treatment-naive period (follow-up 3.6 years), eGFR decline remained modest and stabilized within normal ranges during 4.1 years of treatment (slope difference, 95% CI: -0.13 [-1.15, 0.89] mL/min/1.73m\(^2\)/year, P\(_{pre–post difference}\) = 0.80). Conclusions Cardiac hypertrophy, progressing during pretreatment follow-up, appeared to stabilize during sustained agalsidase beta treatment. eGFR decline remained within normal ranges. This suggests that treatment may prevent further Fabry-related progression of cardiomyopathy in female patients and maintain normal kidney function. KW - Agalsidase beta KW - Enzyme replacement therapy KW - Fabry disease KW - Cardiomyopathy KW - Kidney function KW - Female patients Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235963 VL - 7 IS - 3 ER - TY - JOUR A1 - Barthels, Fabian A1 - Marincola, Gabriella A1 - Marciniak, Tessa A1 - Konhäuser, Matthias A1 - Hammerschmidt, Stefan A1 - Bierlmeier, Jan A1 - Distler, Ute A1 - Wich, Peter R. A1 - Tenzer, Stefan A1 - Schwarzer, Dirk A1 - Ziebuhr, Wilma A1 - Schirmeister, Tanja T1 - Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A JF - ChemMedChem N2 - Staphylococcus aureus is one of the most frequent causes of nosocomial and community‐acquired infections, with drug‐resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active‐site cysteine. A broad series of derivatives were synthesized to derive structure‐activity relationships (SAR). In vitro and in silico methods allowed the experimentally observed binding affinities and selectivities to be rationalized. The most active compounds were found to have single‐digit micromolar Ki values and caused up to a 66 % reduction of S. aureus fibrinogen attachment at an effective inhibitor concentration of 10 μM. This new molecule class exhibited minimal cytotoxicity, low bacterial growth inhibition and impaired sortase‐mediated adherence of S. aureus cells. KW - antibiotics KW - biofilm KW - drug design KW - sortase A Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214581 VL - 15 IS - 10 SP - 839 EP - 850 ER - TY - JOUR A1 - Schmidt, Stefanie A1 - Ebner, Friederike A1 - Rosen, Kerstin A1 - Kniemeyer, Olaf A1 - Brakhage, Axel A. A1 - Löffler, Jürgen A1 - Seif, Michelle A1 - Springer, Jan A1 - Schlosser, Josephine A1 - Scharek‐Tedin, Lydia A1 - Scheffold, Alexander A1 - Bacher, Petra A1 - Kühl, Anja A. A1 - Rösler, Uwe A1 - Hartmann, Susanne T1 - The domestic pig as human‐relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus JF - European Journal of Immunology N2 - Pulmonary mucosal immune response is critical for preventing opportunistic Aspergillus fumigatus infections. Although fungus‐specific CD4\(^{+}\) T cells in blood are described to reflect the actual host–pathogen interaction status, little is known about Aspergillus‐specific pulmonary T‐cell responses. Here, we exploit the domestic pig as human‐relevant large animal model and introduce antigen‐specific T‐cell enrichment in pigs to address Aspergillus‐specific T cells in the lung compared to peripheral blood. In healthy, environmentally Aspergillus‐exposed pigs, the fungus‐specific T cells are detectable in blood in similar frequencies as observed in healthy humans and exhibit a Th1 phenotype. Exposing pigs to 10\(^{6}\) cfu/m\(^{3}\) conidia induces a long‐lasting accumulation of Aspergillus‐specific Th1 cells locally in the lung and also systemically. Temporary immunosuppression during Aspergillus‐exposure showed a drastic reduction in the lung‐infiltrating antifungal T‐cell responses more than 2 weeks after abrogation of the suppressive treatment. This was reflected in blood, but to a much lesser extent. In conclusion, by using the human‐relevant large animal model the pig, this study highlights that the blood clearly reflects the mucosal fungal‐specific T‐cell reactivity in environmentally exposed as well as experimentally exposed healthy pigs. But, immunosuppression significantly impacts the mucosal site in contrast to the initial systemic immune response. KW - fungal aerosolization KW - porcine large animal model KW - pulmonary immune response KW - T cells KW - Aspergillus fumigatus Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216085 VL - 50 IS - 11 SP - 1712 EP - 1728 ER - TY - JOUR A1 - Bangalore, Disha M. A1 - Heil, Hannah S. A1 - Mehringer, Christian F. A1 - Hirsch, Lisa A1 - Hemmen, Katharina A1 - Heinze, Katrin G. A1 - Tessmer, Ingrid T1 - Automated AFM analysis of DNA bending reveals initial lesion sensing strategies of DNA glycosylases JF - Scientific Reports N2 - Base excision repair is the dominant DNA repair pathway of chemical modifications such as deamination, oxidation, or alkylation of DNA bases, which endanger genome integrity due to their high mutagenic potential. Detection and excision of these base lesions is achieved by DNA glycosylases. To investigate the remarkably high efficiency in target site search and recognition by these enzymes, we applied single molecule atomic force microscopy (AFM) imaging to a range of glycosylases with structurally different target lesions. Using a novel, automated, unbiased, high-throughput analysis approach, we were able to resolve subtly different conformational states of these glycosylases during DNA lesion search. Our results lend support to a model of enhanced lesion search efficiency through initial lesion detection based on altered mechanical properties at lesions. Furthermore, its enhanced sensitivity and easy applicability also to other systems recommend our novel analysis tool for investigations of diverse, fundamental biological interactions. KW - atomic-force microscopy KW - base pairs KW - molecular structure KW - crystal structure KW - structural basis KW - repair KW - recognition KW - 8-oxoguanine KW - thymine KW - mismatches Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231338 VL - 10 ER - TY - JOUR A1 - Drakopoulos, Antonios A1 - Decker, Michael T1 - Development and Biological Applications of Fluorescent Opioid Ligands JF - ChemPlusChem N2 - Opioid receptors (ORs) are classified among the oldest and best investigated drug targets due to their fundamental role in the treatment of pain and related disorders. ORs are divided in three conventional subtypes (μ, κ, δ) and the non‐classical nocicepetin receptor. All ORs are family A G protein‐coupled receptors (GPCRs), and are located on the cell surface. Modern biophysical methods use light to investigate physiological processes at organismal, cellular and subcellular level. Many of these methods rely on fluorescent ligands, thus highlighting their importance. This review addresses the advancements in the development of opioid fluorescent ligands and their use in biological, pharmacological and imaging applications. KW - biophysics KW - fluorescent ligands KW - imaging KW - microscopy KW - opioid receptors Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216068 VL - 85 IS - 6 SP - 1354 EP - 1364 ER - TY - JOUR A1 - Bohnert, S. A1 - Monoranu, C. - M. A1 - Siauw, C. A1 - Al-Tinawi, F. A1 - Bohnert, M. T1 - Tödliche Hirnmassenblutung infolge Vitamin-K-Mangels bei einem 9 Wochen alten Säugling JF - Rechtsmedizin N2 - Intrakranielle Blutungen sind im Säuglingsalter seltene, aber lebensbedrohende Ereignisse. Neben Gefäßmissbildungen, Stoffwechseldefekten sowie Störungen der Blutgerinnung kommen v. a. nichtakzidentielle Traumata, Schütteltrauma in Betracht. Die klinische Diagnostik umfasst hinsichtlich der Blutungsgenese neben Sonographie und MRT als apparatives Verfahren auch eine Fundoskopie sowie laborchemische Analysen, insbesondere der Gerinnungsparameter. Für die Blutgerinnung ist das fettlösliche Vitamin K essenziell: Frühe, klassische und späte Vitamin-K-Mangel-Blutungen werden dabei unterschieden. Um ein gehäuftes Wiederauftreten von Vitamin-K-Mangel-Blutungen bei Neugeborenen und jungen Säuglingen zu verhindern, bedarf es einer hinreichenden Aufklärung der Eltern. Eine Verweigerung der Prophylaxe scheint Folge einer weltanschaulich begründeten Ablehnung der Schulmedizin und ein zunehmendes Phänomen in wohlhabenden Industrieländern zu sein. N2 - Intracranial hemorrhages in infants are rare but life-threatening events. Apart from vascular malformations, metabolic disorders and coagulopathies, nonaccidental trauma, in particular shaken baby syndrome must be taken into consideration. Clinical diagnostic tests and procedures to further evaluate the etiology of the hemorrhage include sonography and magnetic resonance imaging (MRI) as imaging procedures as well as fundoscopy and laboratory tests, especially with respect to coagulation parameters. Fat-soluble vitamin K is essential for blood coagulation. A differentiation is made between classical and delayed hemorrhages due to vitamin K deficiency. In order to avoid an increased recurrence of bleeding due to vitamin K deficiency in neonates and young infants, an adequate clarification for the parents is necessary. A refusal of prophylaxis seems to be the result of an ideologically founded rejection of classical medicine and an increasing phenomenon in affluent industrial countries. KW - Intrakranielle Blutung KW - Schütteltrauma KW - Vitamin-K-Mangel-Blutung KW - Prophylaxe KW - intracranial bleeding KW - shaken baby syndrome KW - vitamin k deficiency bleeding KW - prophylaxis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232475 SN - 0937-9819 VL - 30 ER - TY - JOUR A1 - Matthes, Niels A1 - Diers, Johannes A1 - Schlegel, Nicolas A1 - Hankir, Mohammed A1 - Haubitz, Imme A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Validation of MTL30 as a quality indicator for colorectal surgery JF - PLoS One N2 - Background Valid indicators are required to measure surgical quality. These ideally should be sensitive and selective while being easy to understand and adjust. We propose here the MTL30 quality indicator which takes into account 30-day mortality, transfer within 30 days, and a length of stay of 30 days as composite markers of an uneventful operative/postoperative course. Methods Patients documented in the StuDoQ|Colon and StuDoQ|Rectal carcinoma register of the German Society for General and Visceral Surgery (DGAV) were analyzed with regard to the effects of patient and tumor-related risk factors as well as postoperative complications on the MTL30. Results In univariate analysis, the MTL30 correlated significantly with patient and tumor-related risk factors such as ASA score (p<0.001), age (p<0.001), or UICC stage (p<0.001). There was a high sensitivity for the postoperative occurrence of complications such as re-operations (p<0.001) or subsequent bleeding (p<0.001), as well as a significant correlation with the CDC classification (p<0.001). In multivariate analysis, patient-related risk factors and postoperative complications significantly increased the odds ratio for a positive MTL30. A negative MTL30 showed a high specify for an uneventful operative and postoperative course. Conclusion The MTL30 is a valid indicator of colorectal surgical quality. KW - surgical care KW - discharge definition KW - definition KW - mortality KW - pancreatectomy KW - complications KW - superior KW - capture Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230530 VL - 15 IS - 8 ER - TY - JOUR A1 - Mottola, Austin A1 - Schwanfelder, Sonja A1 - Morschhäuser, Joachim T1 - Generation of Viable Candida albicans Mutants Lacking the "Essential" Protein Kinase Snf1 by Inducible Gene Deletion JF - mSphere N2 - The protein kinase Snf1, a member of the highly conserved AMP-activated protein kinase family, is a central regulator of metabolic adaptation. In the pathogenic yeast Candida albicans, Snf1 is considered to be essential, as previous attempts by different research groups to generate homozygous snf1 Delta mutants were unsuccessful. We aimed to elucidate why Snf1 is required for viability in C. albicans by generating snf1 Delta null mutants through forced, inducible gene deletion and observing the terminal phenotype before cell death. Unexpectedly, we found that snf1 Delta mutants were viable and could grow, albeit very slowly, on rich media containing the preferred carbon source glucose. Growth was improved when the cells were incubated at 37 degrees C instead of 30 degrees C, and this phenotype enabled us to isolate homozygous snf1 Delta mutants also by conventional, sequential deletion of both SNF1 alleles in a wild-type C. albicans strain. All snf1 Delta mutants could grow slowly on glucose but were unable to utilize alternative carbon sources. Our results show that, under optimal conditions, C. albicans can live and grow without Snf1. Furthermore, they demonstrate that inducible gene deletion is a powerful method for assessing gene essentiality in C. albicans. IMPORTANCE Essential genes are those that are indispensable for the viability and growth of an organism. Previous studies indicated that the protein kinase Snf1, a central regulator of metabolic adaptation, is essential in the pathogenic yeast Candida albicans, because no homozygous snf1 deletion mutants of C. albicans wild-type strains could be obtained by standard approaches. In order to investigate the lethal consequences of SNF1 deletion, we generated conditional mutants in which SNF1 could be deleted by forced, inducible excision from the genome. Unexpectedly, we found that snf1 null mutants were viable and could grow slowly under optimal conditions. The growth phenotypes of the snf1 Delta mutants explain why such mutants were not recovered in previous attempts. Our study demonstrates that inducible gene deletion is a powerful method for assessing gene essentiality in C. albicans. KW - Candida albicans KW - Snf1 KW - conditional mutants KW - essential genes KW - protein kinases Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230524 VL - 5 IS - 4 ER - TY - JOUR A1 - Voulgari-Kokota, Anna A1 - Steffan-Dewenter, Ingolf A1 - Keller, Alexander T1 - Susceptibility of Red Mason Bee Larvae to Bacterial Threats Due to Microbiome Exchange with Imported Pollen Provisions JF - Insects N2 - Solitary bees are subject to a variety of pressures that cause severe population declines. Currently, habitat loss, temperature shifts, agrochemical exposure, and new parasites are identified as major threats. However, knowledge about detrimental bacteria is scarce, although they may disturb natural microbiomes, disturb nest environments, or harm the larvae directly. To address this gap, we investigated 12 Osmia bicornis nests with deceased larvae and 31 nests with healthy larvae from the same localities in a 16S ribosomal RNA (rRNA) gene metabarcoding study. We sampled larvae, pollen provisions, and nest material and then contrasted bacterial community composition and diversity in healthy and deceased nests. Microbiomes of pollen provisions and larvae showed similarities for healthy larvae, whilst this was not the case for deceased individuals. We identified three bacterial taxa assigned to Paenibacillus sp. (closely related to P. pabuli/amylolyticus/xylanexedens), Sporosarcina sp., and Bacillus sp. as indicative for bacterial communities of deceased larvae, as well as Lactobacillus for corresponding pollen provisions. Furthermore, we performed a provisioning experiment, where we fed larvae with untreated and sterilized pollens, as well as sterilized pollens inoculated with a Bacillus sp. isolate from a deceased larva. Untreated larval microbiomes were consistent with that of the pollen provided. Sterilized pollen alone did not lead to acute mortality, while no microbiome was recoverable from the larvae. In the inoculation treatment, we observed that larval microbiomes were dominated by the seeded bacterium, which resulted in enhanced mortality. These results support that larval microbiomes are strongly determined by the pollen provisions. Further, they underline the need for further investigation of the impact of detrimental bacterial acquired via pollens and potential buffering by a diverse pollen provision microbiome in solitary bees. KW - Osmia bicornis KW - solitary bee KW - bacterial transmission KW - microbiome KW - pollen provisions KW - pathogen KW - secondary invader KW - Paenibacillus KW - Bacillus KW - Sporosarcina Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207948 SN - 2075-4450 VL - 11 IS - 6 ER - TY - JOUR A1 - Reichel, Alexandra A1 - Röding, Kristina A1 - Stoevesandt, Johanna A1 - Trautmann, Axel T1 - De‐labelling antibiotic allergy through five key questions JF - Clinical & Experimental Allergy KW - allergy KW - antibiotic KW - algorithm Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215508 VL - 50 IS - 4 SP - 532 EP - 535 ER - TY - JOUR A1 - Glaser, Kirsten A1 - Speer, Christian P. A1 - Wright, Clyde J. T1 - Fine tuning non-invasive respiratory support to prevent lung injury in the extremely premature infant JF - Frontiers in Pediatrics N2 - Within the last decades, therapeutic advances, such as antenatal corticosteroids, surfactant replacement, monitored administration of supplemental oxygen, and sophisticated ventilatory support have significantly improved the survival of extremely premature infants. In contrast, the incidence of some neonatal morbidities has not declined. Rates of bronchopulmonary dysplasia (BPD) remain high and have prompted neonatologists to seek effective strategies of non-invasive respiratory support in high risk infants in order to avoid harmful effects associated with invasive mechanical ventilation. There has been a stepwise replacement of invasive mechanical ventilation by early continuous positive airway pressure (CPAP) as the preferred strategy for initial stabilization and for early respiratory support of the premature infant and management of respiratory distress syndrome. However, the vast majority of high risk babies are mechanically ventilated at least once during their NICU stay. Adjunctive therapies aiming at the prevention of CPAP failure and the support of functional residual capacity have been introduced into clinical practice, including alternative techniques of administering surfactant as well as non-invasive ventilation approaches. In contrast, the strategy of applying sustained lung inflations in the delivery room has recently been abandoned due to evidence of higher rates of death within the first 48 h of life. KW - preterm infant KW - respiratory distress syndrome (RDS) KW - lung injury KW - bronchopulmonary dysplasia (BPD) KW - non-invasive ventilation KW - non-invasive respiratory support KW - continuous positive airway pressure (CPAP) KW - sustained lung inflation (SLI) Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193762 SN - 2296-2360 VL - 7 ER - TY - JOUR A1 - Cosarinsky, Marcela I. A1 - Römer, Daniela A1 - Roces, Flavio T1 - Nest Turrets of Acromyrmex Grass-Cutting Ants: Micromorphology Reveals Building Techniques and Construction Dynamics JF - Insects N2 - Acromyrmex fracticornis grass-cutting ants construct conspicuous chimney-shaped nest turrets made of intermeshed grass fragments. We asked whether turrets are constructed by merely piling up nearby materials around the entrance, or whether ants incorporate different materials as the turret develops. By removing the original nest turrets and following their rebuilding process over three consecutive days, age-dependent changes in wall morphology and inner lining fabrics were characterized. Micromorphological descriptions based on thin sections of turret walls revealed the building behaviors involved. Ants started by collecting nearby twigs and dry grass fragments that are piled up around the nest entrance. Several large fragments held the structure like beams. As a net-like structure grew, soil pellets were placed in between the intermeshed plant fragments from the turret base to the top, reinforcing the structure. Concomitantly, the turret inner wall was lined with soil pellets, starting from the base. Therefore, the consolidation of the turret occurred both over time and from its base upwards. It is argued that nest turrets do not simply arise by the arbitrary deposition of nearby materials, and that workers selectively incorporate large materials at the beginning, and respond to the developing structure by reinforcing the intermeshed plant fragments over time. KW - building behavior KW - Acromyrmex fracticornis KW - leaf-cutting ants KW - collective pattern KW - architecture KW - self-organization KW - microstructure KW - material composition KW - thin sections Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200680 SN - 2075-4450 VL - 11 IS - 2 ER - TY - JOUR A1 - Riedl, Katharina A. A1 - Kampf, Thomas A1 - Herold, Volker A1 - Behr, Volker C. A1 - Bauer, Wolfgang R. T1 - Wall shear stress analysis using 17.6 Tesla MRI: A longitudinal study in ApoE\(^{-/-}\)mice with histological analysis JF - PLoS One N2 - This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE\(^{-/-}\)mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. Allin vivoMR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based "Flow Tool". The body weight of ApoE\(^{-/-}\)mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis. KW - phase-contrast MRI KW - flow patterns KW - blood flow KW - apolipoprotein-E KW - atheriosclerosis KW - mouse KW - mice KW - quantification KW - association KW - lesions Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229318 VL - 15 IS - 8 ER - TY - JOUR A1 - Koepsell, Hermann T1 - Glucose transporters in brain in health and disease JF - Pflügers Archiv - European Journal of Physiology N2 - Energy demand of neurons in brain that is covered by glucose supply from the blood is ensured by glucose transporters incapillaries and brain cells. In brain, the facilitative diffusion glucose transporters GLUT1-6 and GLUT8, and the Na+-D-glucosecotransporters SGLT1 are expressed. The glucose transporters mediate uptake of D-glucose across the blood-brain barrier anddelivery of D-glucose to astrocytes and neurons. They are critically involved in regulatory adaptations to varying energy demandsin response to differing neuronal activities and glucose supply. In this review, a comprehensive overview about verified andproposed roles of cerebral glucose transporters during health and diseases is presented. Our current knowledge is mainly based onexperiments performed in rodents. First, the functional properties of human glucose transporters expressed in brain and theircerebral locations are described. Thereafter, proposed physiological functions of GLUT1, GLUT2, GLUT3, GLUT4, andSGLT1 for energy supply to neurons, glucose sensing, central regulation of glucohomeostasis, and feeding behavior are compiled, and their roles in learning and memory formation are discussed. In addition, diseases are described in which functionalchanges of cerebral glucose transporters are relevant. These are GLUT1 deficiency syndrome (GLUT1-SD), diabetes mellitus, Alzheimer’s disease (AD), stroke, and traumatic brain injury (TBI). GLUT1-SD is caused by defect mutations in GLUT1. Diabetes and AD are associated with changed expression of glucose transporters in brain, and transporter-related energy defi-ciency of neurons may contribute to pathogenesis of AD. Stroke and TBI are associated with changes of glucose transporter expression that influence clinical outcome KW - glucosetransporter KW - brain KW - GLUT1 KW - GLUT2 KW - GLUT3 KW - GLUT4 KW - SGLT1 KW - diabetes KW - Parkinson’s disease KW - stroke Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232746 SN - 0031-6768 VL - 472 ER - TY - JOUR A1 - Bell, Luisa A1 - Lenhart, Alexander A1 - Rosenwald, Andreas A1 - Monoranu, Camelia M. A1 - Berberich-Siebelt, Friederike T1 - Lymphoid aggregates in the CNS of progressive multiple sclerosis patients lack regulatory T cells JF - Frontiers in Immunology N2 - In gray matter pathology of multiple sclerosis, neurodegeneration associates with a high degree of meningeal inflammatory activity. Importantly, ectopic lymphoid follicles (eLFs) were identified at the inflamed meninges of patients with progressive multiple sclerosis. Besides T lymphocytes, they comprise B cells and might elicit germinal center (GC)-like reactions. GC reactions are controlled by FOXP3+ T-follicular regulatory cells (TFR), but it is unknown if they participate in autoantibody production in eLFs. Receiving human post-mortem material, gathered from autopsies of progressive multiple sclerosis patients, indeed, distinct inflammatory infiltrates enriched with B cells could be detected in perivascular areas and deep sulci. CD35+ cells, parafollicular CD138+ plasma cells, and abundant expression of the homing receptor for GCs, CXCR5, on lymphocytes defined some of them as eLFs. However, they resembled GCs only in varying extent, as T cells did not express PD-1, only few cells were positive for the key transcriptional regulator BCL-6 and ongoing proliferation, whereas a substantial number of T cells expressed high NFATc1 like GC-follicular T cells. Then again, predominant cytoplasmic NFATc1 and an enrichment with CD3+CD27+ memory and CD4+CD69+ tissue-resident cells implied a chronic state, very much in line with PD-1 and BCL-6 downregulation. Intriguingly, FOXP3+ cells were almost absent in the whole brain sections and CD3+FOXP3+ TFRs were never found in the lymphoid aggregates. This also points to less controlled humoral immune responses in those lymphoid aggregates possibly enabling the occurrence of CNS-specific autoantibodies in multiple sclerosis patients. KW - ectopic lymphoid follicle KW - lymphoid aggregate KW - T-follicular regulatory cell KW - meningeal inflammation KW - NFATc1 KW - progressive multiple sclerosis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198130 SN - 1664-3224 VL - 10 IS - 3090 ER - TY - JOUR A1 - Nandi, Corina A1 - Crombach, Anselm A1 - Elbert, Thomas A1 - Bambonye, Manassé A1 - Pryss, Rüdiger A1 - Schobel, Johannes A1 - Weierstall‐Pust, Roland T1 - The cycle of violence as a function of PTSD and appetitive aggression: A longitudinal study with Burundian soldiers JF - Aggressive Behavior N2 - During deployment, soldiers face situations in which they are not only exposed to violence but also have to perpetrate it themselves. This study investigates the role of soldiers' levels of posttraumatic stress disorder (PTSD) symptoms and appetitive aggression, that is, a lust for violence, for their engaging in violence during deployment. Furthermore, factors during deployment influencing the level of PTSD symptoms and appetitive aggression after deployment were examined for a better comprehension of the maintenance of violence. Semi‐structured interviews were conducted with 468 Burundian soldiers before and after a 1‐year deployment to Somalia. To predict violent acts during deployment (perideployment) as well as appetitive aggression and PTSD symptom severity after deployment (postdeployment), structural equation modeling was utilized. Results showed that the number of violent acts perideployment was predicted by the level of appetitive aggression and by the severity of PTSD hyperarousal symptoms predeployment. In addition to its association with the predeployment level, appetitive aggression postdeployment was predicted by violent acts and trauma exposure perideployment as well as positively associated with unit support. PTSD symptom severity postdeployment was predicted by the severity of PTSD avoidance symptoms predeployment and trauma exposure perideployment, and negatively associated with unit support. This prospective study reveals the importance of appetitive aggression and PTSD hyperarousal symptoms for the engagement in violent acts during deployment, while simultaneously demonstrating how these phenomena may develop in mutually reinforcing cycles in a war setting. KW - aggression KW - deployment KW - PTSD KW - soldiers KW - violence Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218235 VL - 46 IS - 5 SP - 391 EP - 399 ER - TY - JOUR A1 - Mahl, Magnus A1 - Shoyama, Kazutaka A1 - Krause, Ana‐Maria A1 - Schmidt, David A1 - Würthner, Frank T1 - Base‐Assisted Imidization: A Synthetic Method for the Introduction of Bulky Imide Substituents to Control Packing and Optical Properties of Naphthalene and Perylene Imides JF - Angewandte Chemie International Edition N2 - We report the direct imidization of naphthalene and perylene dicarboxylic anhydrides/esters with bulky ortho,ortho‐diaryl‐ and ortho,ortho‐dialkynylaniline derivatives. This imidization method uses n‐butyllithium as a strong base to increase the reactivity of bulky amine derivatives, proceeds under mild reaction conditions, requires only stoichiometric amounts of reactants and gives straightforward access to new sterically crowded rylene dicarboximides. Mechanistic investigations suggest an isoimide as intermediary product, which was converted to the corresponding imide upon addition of an aqueous base. Single‐crystal X‐ray diffraction analyses reveal dimeric packing motifs for monoimides, while two‐side shielded bisimides crystallize in isolated molecules without close π–π‐interactions. Spectroscopic investigations disclose the influence of the bulky substituents on the optical properties in the solid state. KW - dyes KW - fluorescence KW - imidization KW - perylene imide KW - solid-state emitters Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218246 VL - 59 IS - 32 SP - 13401 EP - 13405 ER - TY - JOUR A1 - Hann, Alexander A1 - Graf, Louisa A1 - Seufferlein, Thomas A1 - Zizer, Eugen T1 - Gastrointestinal Bleeding Diagnosed by Capsule Endoscopy – A Change towards More Patients with Bleeding-related Drugs JF - Journal of Advances in Medicine and Medical Research N2 - Background: Video capsule endoscopy (VCE) is the standard procedure for a work-up of a suspected bleeding source after negative gastroscopy and colonoscopy. Popularity of this procedure increased in the last decade. In this work we aimed to identify the changes in patient characteristics and how those changes influence bleeding related findings. In particular the assumed higher risk of gastrointestinal bleeding of the new oral anticoagulants (nOAC) compared to phenprocoumon was of interest. Methods: Consecutive VCE examinations performed at our center from January 2004 to March 2018 were identified retrospectively. Baseline characteristics of the patients, VCE results and treatment that was initiated were analyzed. Results: 560 VCE were included in the analysis. The rate of VCE per month increased from 2.3/month in the period of January 2004 – December 2012 up to 5.0/month in January 2013 – March 2018. Accompanied by this increase the examined patients suffered from significantly more comorbidities (72 vs. 82%, p 0.001) and used a higher number of bleeding-related drugs (47 vs. 66%, p <0.001), especially nOACs. Age above 65 and bleeding-related drugs were significantly associated with angiodysplasias found on VCE examinations. NOACs and phenprocoumon showed no difference in their correlation to angiodysplasias. Conclusion: This single center retrospective analysis revealed a steep increase in VCE examinations over the last years with an increase in the prevalence of comorbidities and the use of bleeding-related drugs. Interestingly, use of both nOACs and phenprocoumon did not result in a significant higher rate of angiodysplasias in the VCE. KW - video capsule endoscopy KW - small bowel bleeding KW - nOAC KW - VCE Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256687 SN - 2456-8899 VL - 32 IS - 19 ER - TY - JOUR A1 - Appelt‐Menzel, Antje A1 - Oerter, Sabrina A1 - Mathew, Sanjana A1 - Haferkamp, Undine A1 - Hartmann, Carla A1 - Jung, Matthias A1 - Neuhaus, Winfried A1 - Pless, Ole T1 - Human iPSC‐Derived Blood‐Brain Barrier Models: Valuable Tools for Preclinical Drug Discovery and Development? JF - Current Protocols in Stem Cell Biology N2 - Translating basic biological knowledge into applications remains a key issue for effectively tackling neurodegenerative, neuroinflammatory, or neuroendocrine disorders. Efficient delivery of therapeutics across the neuroprotective blood‐brain barrier (BBB) still poses a demanding challenge for drug development targeting central nervous system diseases. Validated in vitro models of the BBB could facilitate effective testing of drug candidates targeting the brain early in the drug discovery process during lead generation. We here review the potential of mono‐ or (isogenic) co‐culture BBB models based on brain capillary endothelial cells (BCECs) derived from human‐induced pluripotent stem cells (hiPSCs), and compare them to several available BBB in vitro models from primary human or non‐human cells and to rodent in vivo models, as well as to classical and widely used barrier models [Caco‐2, parallel artificial membrane permeability assay (PAMPA)]. In particular, we are discussing the features and predictivity of these models and how hiPSC‐derived BBB models could impact future discovery and development of novel CNS‐targeting therapeutics. KW - blood‐brain barrier (BBB) KW - CNS disease KW - drug permeability screening KW - human‐induced pluripotent stem cells (hiPSC) KW - preclinical drug discovery Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218509 VL - 55 IS - 1 ER - TY - JOUR A1 - Merz, Maximilian A1 - Dechow, Tobias A1 - Scheyt, Mithun A1 - Schmidt, Christian A1 - Knop, Stefan T1 - The clinical management of lenalidomide-based therapy in patients with newly diagnosed multiple myeloma JF - Annals of Hematology N2 - Lenalidomide is an integral, yet evolving, part of current treatment pathways for both transplant-eligible and transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). It is approved in combination with dexamethasone as first-line therapy for transplant-ineligible patients with NDMM, and as maintenance treatment following autologous stem cell transplantation (ASCT). Although strong clinical trial evidence has supported the integration of lenalidomide into current treatment paradigms for NDMM, applying those paradigms to individual patients and determining which patients are most likely to benefit from lenalidomide treatment are more complex. In this paper, we utilize the available clinical trial evidence to provide recommendations for patient selection and lenalidomide dosing in both the first-line setting in patients ineligible for ASCT and the maintenance setting in patients who have undergone ASCT. In addition, we provide guidance on management of those adverse events that are most commonly associated with lenalidomide treatment, and consider the optimal selection and sequencing of next-line agents following long-term frontline or maintenance treatment with lenalidomide. KW - adverse events KW - lenalidomide KW - multiple myeloma KW - newly diagnosed KW - safety Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231862 SN - 0939-5555 VL - 99 ER - TY - JOUR A1 - Metje-Sprink, Janina A1 - Groffmann, Johannes A1 - Neumann, Piotr A1 - Barg-Kues, Brigitte A1 - Ficner, Ralf A1 - Kühnel, Karin A1 - Schalk, Amanda M. A1 - Binotti, Beyenech T1 - Crystal structure of the Rab33B/Atg16L1 effector complex JF - Scientific Reports N2 - The Atg12-Atg5/Atg16L1 complex is recruited by WIPI2b to the site of autophagosome formation. Atg16L1 is an effector of the Golgi resident GTPase Rab33B. Here we identified a minimal stable complex of murine Rab33B(30-202) Q92L and Atg16L1(153-210). Atg16L1(153-210) comprises the C-terminal part of the Atg16L1 coiled-coil domain. We have determined the crystal structure of the Rab33B Q92L/Atg16L1(153-210) effector complex at 3.47 angstrom resolution. This structure reveals that two Rab33B molecules bind to the diverging alpha -helices of the dimeric Atg16L1 coiled-coil domain. We mutated Atg16L1 and Rab33B interface residues and found that they disrupt complex formation in pull-down assays and cellular co-localization studies. The Rab33B binding site of Atg16L1 comprises 20 residues and immediately precedes the WIPI2b binding site. Rab33B mutations that abolish Atg16L binding also abrogate Rab33B association with the Golgi stacks. Atg16L1 mutants that are defective in Rab33B binding still co-localize with WIPI2b in vivo. The close proximity of the Rab33B and WIPI2b binding sites might facilitate the recruitment of Rab33B containing vesicles to provide a source of lipids during autophagosome biogenesis. KW - autophagosome formation KW - ATG12-ATG5 conjugate KW - LC3 lipidation KW - binding sites KW - ATG proteins KW - RAB GTPases KW - family KW - membrane KW - recognition KW - proppins Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230396 VL - 10 ER - TY - JOUR A1 - Doerfler, Inken A1 - Cadotte, Marc W. A1 - Weisser, Wolfgang W. A1 - Müller, Jörg A1 - Gossner, Martin M. A1 - Heibl, Christoph A1 - Bässler, Claus A1 - Thorn, Simon A1 - Seibold, Sebastian T1 - Restoration‐oriented forest management affects community assembly patterns of deadwood‐dependent organisms JF - Journal of Applied Ecology N2 - Land‐use intensification leads to loss and degradation of habitats and is thus a major driver of biodiversity loss. Restoration strategies typically focus on promoting biodiversity but often neglect that land‐use intensification could have changed the underlying mechanisms of community assembly. Since assembly mechanisms determine the diversity and composition of communities, we propose that evaluation of restoration strategies should consider effects of restoration on biodiversity and community assembly. Using a multi‐taxon approach, we tested whether a strategy that promotes forest biodiversity by restoring deadwood habitats also affects assembly patterns. We assessed saproxylic (i.e. deadwood‐dependent) beetles and fungi, as well as non‐saproxylic plants and birds in 68 beech forest plots in southern Germany, 8 years after the commencement of a restoration project. To assess changes in community assembly, we analysed the patterns of functional–phylogenetic diversity, community‐weighted mean (CWM) traits and their diversity. We hypothesized that restoration increases habitat amount and heterogeneity of deadwood and reduces canopy cover and thereby decreases the strength of environmental filters imposed by past silvicultural intensification, such as a low amount in deadwood. With the restoration of deadwood habitats, saproxylic beetle communities became less functionally–phylogenetically similar, whereas the assembly patterns of saproxylic fungi and non‐saproxylic taxa remained unaffected by deadwood restoration. Among the traits analysed, deadwood diameter niche position of species was most strongly affected indicating that the enrichment of large deadwood objects led to lower functional–phylogenetical similarity of saproxylic beetles. Community assembly and traits of plants were mainly influenced by microclimate associated with changes in canopy cover. Synthesis and applications. Our results indicate that the positive effects of deadwood restoration on saproxylic beetle richness are associated with an increase in deadwood amount. This might be linked to an increase in deadwood heterogeneity, and therefore decreasing management‐induced environmental filters. Deadwood enrichment can thus be considered an effective restoration strategy which reduces the negative effects of intense forest management on saproxylic taxa by not only promoting biodiversity but also by decreasing the environmental filters shaping saproxylic beetle communities, thus allowing the possibly for more interactions between species and a higher functional diversity. KW - assembly mechanisms KW - beech forest KW - community‐weighted mean KW - deadwood enrichment KW - habitat heterogeneity KW - restoration strategy KW - saproxylic species KW - species traits Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217918 VL - 57 IS - 12 SP - 2429 EP - 2440 ER - TY - JOUR A1 - Di Sante, Domenico A1 - Erdmenger, Johanna A1 - Greiter, Martin A1 - Matthaiakakis, Ioannis A1 - Meyer, René A1 - Fernandez, David Rodríguez A1 - Thomale, Ronny A1 - van Loon, Erik A1 - Wehling, Tim T1 - Turbulent hydrodynamics in strongly correlated Kagome metals JF - Nature Communications N2 - A current challenge in condensed matter physics is the realization of strongly correlated, viscous electron fluids. These fluids can be described by holography, that is, by mapping them onto a weakly curved gravitational theory via gauge/gravity duality. The canonical system considered for realizations has been graphene. In this work, we show that Kagome systems with electron fillings adjusted to the Dirac nodes provide a much more compelling platform for realizations of viscous electron fluids, including non-linear effects such as turbulence. In particular, we find that in Scandium Herbertsmithite, the fine-structure constant, which measures the effective Coulomb interaction, is enhanced by a factor of about 3.2 as compared to graphene. We employ holography to estimate the ratio of the shear viscosity over the entropy density in Sc-Herbertsmithite, and find it about three times smaller than in graphene. These findings put the turbulent flow regime described by holography within the reach of experiments. Viscous electron fluids are predicted in strongly correlated systems but remain challenging to realize. Here, the authors predict enhanced effective Coulomb interaction and reduced ratio of the shear viscosity over entropy density in a Kagome metal, inferring turbulent flow of viscous electron fluids. KW - coupling-constant dependence KW - shear viscosity KW - electron KW - resistance Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230380 VL - 11 ER - TY - JOUR A1 - Nattmann, Anja A1 - Breun, Maria A1 - Monoranu, Camelia M. A1 - Matthies, Cordula A1 - Ernestus, Ralf-Ingo A1 - Löhr, Mario A1 - Hagemann, Carsten T1 - Analysis of ADAM9 regulation and function in vestibular schwannoma primary cells JF - BMC Research Notes N2 - Objective Recently, we described a disintegrin and metalloproteinase 9 (ADAM9) overexpression by Schwann cells of vestibular schwannoma (VS) and suggested that it might be a marker for VS tumor growth and invasiveness. This research note provides additional data utilizing a small cohort of VS primary cultures and tissue samples. We examined whether reconstitution of Merlin expression in VS cells regulates ADAM9 protein expression and performed lentiviral ADAM9 knock down to investigate possible effects on VS cells numbers. Moreover, the co-localization of ADAM9 and Integrins α6 and α2β1, respectively, was examined by immunofluorescence double staining. Results ADAM9 expression was not regulated by Merlin in VS. However, ADAM9 knock down led to 58% reduction in cell numbers in VS primary cell cultures (p < 0.0001). While ADAM9 and Integrin α2β1 were co-localized in only 22% (2 of 9) of VS, ADAM9 and Integrin α6 were co-localized in 91% (10 of 11) of VS. Therefore, we provide first observations on possible regulatory functions of ADAM9 expression in VS. KW - vestibular schwannoma KW - pathogenesis KW - ADAM9 KW - knock down KW - integrin KW - immunofuorescence double staining KW - Merlin KW - primary cell culture Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231213 VL - 13 ER - TY - JOUR A1 - Meybohm, Patrick A1 - Straub, Niels A1 - Füllenbach, Christoph A1 - Judd, Leonie A1 - Kleinerüschkamp, Adina A1 - Taeuber, Isabel A1 - Zacharowski, Kai A1 - Choorapoikayil, Suma T1 - Health economics of Patient Blood Management: a cost‐benefit analysis based on a meta‐analysis JF - Vox Sanguinis N2 - Background and Objectives Patient Blood Management (PBM) is the timely application of evidence‐based medical and surgical concepts designed to improve haemoglobin concentration, optimize haemostasis and minimize blood loss in an effort to improve patient outcomes. The focus of this cost‐benefit analysis is to analyse the economic benefit of widespread implementation of a multimodal PBM programme. Materials and Methods Based on a recent meta‐analysis including 17 studies (>235 000 patients) comparing PBM with control care and data from the University Hospital Frankfurt, a cost‐benefit analysis was performed. Outcome data were red blood cell (RBC) transfusion rate, number of transfused RBC units, and length of hospital stay (LOS). Costs were considered for the following three PBM interventions as examples: anaemia management including therapy of iron deficiency, use of cell salvage and tranexamic acid. For sensitivity analysis, a Monte Carlo simulation was performed. Results Iron supplementation was applied in 3·1%, cell salvage in 65% and tranexamic acid in 89% of the PBM patients. In total, applying these three PBM interventions costs €129·04 per patient. However, PBM was associated with a reduction in transfusion rate, transfused RBC units per patient, and LOS which yielded to mean savings of €150·64 per patient. Thus, the overall benefit of PBM implementation was €21·60 per patient. In the Monte Carlo simulation, the cost savings on the outcome side exceeded the PBM costs in approximately 2/3 of all repetitions and the total benefit was €1 878 000 in 100·000 simulated patients. Conclusion Resources to implement a multimodal PBM concept optimizing patient care and safety can be cost‐effectively. KW - Patient Blood Management (PBM) KW - haemoglobin concentration KW - haemostasis KW - blood loss Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214084 VL - 115 IS - 2 SP - 182 EP - 188 ER - TY - JOUR A1 - Berger, Constantin A1 - Zdzieblo, Daniela T1 - Glucose transporters in pancreatic islets JF - Pflügers Archiv - European Journal of Physiology N2 - The fine-tuning of glucose uptake mechanisms is rendered by various glucose transporters with distinct transportcharacteristics. In the pancreatic islet, facilitative diffusion glucose transporters (GLUTs), and sodium-glucosecotransporters (SGLTs) contribute to glucose uptake and represent important components in the glucose-stimulatedhormone release from endocrine cells, therefore playing a crucial role in blood glucose homeostasis. This reviewsummarizes the current knowledge aboutcell type-specific expression profiles as well as proven and putative functionsof distinct GLUT and SGLT family members in the human and rodent pancreatic islet and further discusses their possibleinvolvement in onset and progression ofdiabetes mellitus. In context of GLUTs, we focus on GLUT2, characterizing themain glucose transporter in insulin-secretingβ-cells in rodents. In addition, we discuss recent data proposing that otherGLUT family members, namely GLUT1 and GLUT3, render this task in humans. Finally, we summarize latest infor-mation about SGLT1 and SGLT2 as representatives of the SGLT family that have been reported to be expressed predominantly in the α-cell population with a suggested functional role in the regulation of glucagon release KW - Glucose transport KW - Pancreatic islet KW - β-Cell KW - α-Cell KW - GLUTs KW - SGLTs Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232738 SN - 0031-6768 VL - 472 ER - TY - JOUR A1 - Kölbel, Heike A1 - Roos, Andreas A1 - van der Ven, Peter F. M. A1 - Evangelista, Teresinha A1 - Nolte, Kay A1 - Johnson, Katherine A1 - Töpf, Ana A1 - Wilson, Michael A1 - Kress, Wolfram A1 - Sickmann, Albert A1 - Straub, Volker A1 - Kollipara, Laxmikanth A1 - Weis, Joachim A1 - Fürst, Dieter O. A1 - Schara, Ulrike T1 - First clinical and myopathological description of a myofibrillar myopathy with congenital onset and homozygous mutation in FLNC JF - Human Mutation N2 - Filamin C (encoded by the FLNC gene) is a large actin‐cross‐linking protein involved in shaping the actin cytoskeleton in response to signaling events both at the sarcolemma and at myofibrillar Z‐discs of cross‐striated muscle cells. Multiple mutations in FLNC are associated with myofibrillar myopathies of autosomal‐dominant inheritance. Here, we describe for the first time a boy with congenital onset of generalized muscular hypotonia and muscular weakness, delayed motor development but no cardiac involvement associated with a homozygous FLNC mutation c.1325C>G (p.Pro442Arg). We performed ultramorphological, proteomic, and functional investigations as well as immunological studies of known marker proteins for dominant filaminopathies. We show that the mutant protein is expressed in similar quantities as the wild‐type variant in control skeletal muscle fibers. The proteomic signature of quadriceps muscle is altered and ultrastructural perturbations are evident. Moreover, filaminopathy marker proteins are comparable both in our homozygous and a dominant control case (c.5161delG). Biochemical investigations demonstrate that the recombinant mutant protein is less stable and more prone to degradation by proteolytic enzymes than the wild‐type variant. The unusual congenital presentation of the disease clearly demonstrates that homozygosity for mutations in FLNC severely aggravates the phenotype. KW - congenital myopathy KW - filamin C KW - myofibrillar myopathy KW - proteomic signature KW - recessive inheritance Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215481 VL - 41 IS - 9 SP - 1600 EP - 1614 ER - TY - JOUR A1 - Schrüfer, Philipp A1 - Brockow, Knut A1 - Stoevesandt, Johanna A1 - Trautmann, Axel T1 - Predominant patterns of beta-lactam hypersensitivity in a single German Allergy Center: exanthem induced by aminopenicillins, anaphylaxis by cephalosporins JF - Allergy, Asthma & Clinical Immunology N2 - Background Penicillins and other beta-lactam antibiotics are the most common elicitors of allergic drug reaction. However, data on the pattern of clinical reaction types elicited by specific beta-lactams are scarce and inconsistent. We aimed to determine patterns of beta-latam allergy, i.e. the association of a clinical reaction type with a specific beta-lactam antibiotic. Methods We retrospectively evaluated data from 800 consecutive patients with suspected beta-lactam hypersensitivity over a period of 11 years in a single German Allergy Center. Results beta-lactam hypersensitivity was definitely excluded in 595 patients, immediate-type (presumably IgE-mediated) hypersensitivity was diagnosed in 70 and delayed-type hypersensitivity in 135 cases. Most (59 out of 70, 84.3%) immediate-type anaphylactic reactions were induced by a limited number of cephalosporins. Delayed reactions were regularly caused by an aminopenicillin (127 out of 135, 94.1%) and usually manifested as a measles-like exanthem (117 out of 135, 86.7%). Intradermal testing proved to be the most useful method for diagnosing beta-lactam allergy, but prick testing was already positive in 24 out of 70 patients with immediate-type hypersensitivity (34.3%). Patch testing in addition to intradermal testing did not provide additional information for the diagnosis of delayed-type hypersensitivity. Almost all beta-lactam allergic patients tolerated at least one, usually several alternative substances out of the beta-lactam group. Conclusions We identified two patterns of beta-lactam hypersensitivity: aminopenicillin-induced exanthem and anaphylaxis triggered by certain cephalosporins. Intradermal skin testing was the most useful method to detect both IgE-mediated and delayed-type beta-lactam hypersensitivity. KW - amoxicillin KW - ampicillin KW - angioedema KW - drug adverse reaction KW - drug allergy KW - drug hypersensitivity KW - penicillin allergy KW - penicillin hypersensitivity KW - urticaria Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231306 VL - 16 ER - TY - JOUR A1 - Jellinghaus, Katharina A1 - Scherer, Charlotte A1 - Stauffer, Edouard A1 - Urban, Petra A1 - Bohnert, Michael A1 - Kneubuehl, Beat P. T1 - Deadly injuries through recoilless anti-tank weapons while military shooting practice — two case studies from Germany and Switzerland JF - International Journal of Legal Medicine N2 - In this casuistry, two accidents from Germany and Switzerland are presented that happened during the shot of recoilless anti-tankweapons. In both cases, the injuries led to the death of two soldiers: A 22-year-old soldier in Germany was struck by the countermass of a so-called Davis gun which had been fired by a comrade during a firing exercise; he died from his severe injuries,especially in the abdominal part of the body. As a peculiarity of the wound morphology, it was found to be a thick-layered,metallic, gray material in the wound cavity, which corresponded to the material of the counter mass that was ejected opposite tothe shooting direction. The other case took place in Switzerland, where a 24-year-old soldier was seriously injured during anexercise with portable anti-tank rockets. At the time the shot was fired, he stood behind the launcher and was hit by the propulsionjet of the rocket motor. He died as well from his severe injuries, which were located at the chest done by the gas jet and by the veryhigh pressure. In both cases, two different causes of death were present: massive blunt violence in the first case versus a jet of hotgases of very high speed and temperature in the second case. KW - Anti-tank weapon KW - Military shooting KW - Davis gun KW - Anti-tank rocket KW - Ballistics Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232727 SN - 0937-9827 VL - 134 ER - TY - JOUR A1 - Zullo, Alberto A1 - Fleckenstein, Johannes A1 - Schleip, Robert A1 - Hoppe, Kerstin A1 - Wearing, Scott A1 - Klingler, Werner T1 - Structural and Functional Changes in the Coupling of Fascial Tissue, Skeletal Muscle, and Nerves During Aging JF - Frontiers in Physiology N2 - Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair. KW - aging KW - connective tissue KW - fascia KW - skeletal muscle KW - nerve Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206890 SN - 1664-042X VL - 11 IS - 592 ER - TY - JOUR A1 - Bittorf, Patrick A1 - Bergmann, Thorsten A1 - Merlin, Simone A1 - Olgasi, Chistina A1 - Pullig, Oliver A1 - Sanzenbacher, Ralf A1 - Zierau, Martin A1 - Walles, Heike A1 - Follenzi, Antonia A1 - Braspenning, Joris T1 - Regulatory-Compliant Validation of a Highly Sensitive qPCR for Biodistribution Assessment of Hemophilia A Patient Cells JF - Molecular Therapy - Methods & Clinical Development N2 - The investigation of the biodistribution profile of a cell-based medicinal product is a pivotal prerequisite to allow a factual benefit-risk assessment within the non-clinical to clinical translation in product development. Here, a qPCR-based method to determine the amount of human DNA in mouse DNA was validated according to the guidelines of the European Medicines Agency and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Furthermore, a preclinical worst-case scenario study was performed in which this method was applied to investigate the biodistribution of 2 x 10\(^6\) intravenously administered, genetically modified, blood outgrowth endothelial cells from hemophilia A patients after 24 h and 7 days. The validation of the qPCR method demonstrated high accuracy, precision, and linearity for the concentration interval of 1:1 x 10\(^3\) to 1:1 x 10\(^6\) human to mouse DNA. The application of this method in the biodistribution study resulted in the detection of human genomes in four out of the eight investigated organs after 24 h. After 7 days, no human DNA was detected in the eight organs analyzed. This biodistribution study provides mandatory data on the toxicokinetic safety profile of an actual candidate cell-based medicinal product. The extensive evaluation of the required validation parameters confirms the applicability of the qPCR method for non-clinical biodistribution studies. KW - outgrowth endothelial cells KW - real time PCR KW - in vivo KW - gene therapy KW - factor-VIII KW - murine KW - quantification KW - establishment KW - phenotype KW - xenotransplantation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230284 VL - 18 ER - TY - JOUR A1 - Fazeli, Gholamreza A1 - Beer, Katharina B. A1 - Geisenhof, Michaela A1 - Tröger, Sarah A1 - König, Julia A1 - Müller-Reichert, Thomas A1 - Wehman, Ann M. T1 - Loss of the Major Phosphatidylserine or Phosphatidylethanolamine Flippases Differentially Affect Phagocytosis JF - Frontiers in Cell and Developmental Biology N2 - The lipids phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEth) are normally asymmetrically localized to the cytosolic face of membrane bilayers, but can both be externalized during diverse biological processes, including cell division, cell fusion, and cell death. Externalized lipids in the plasma membrane are recognized by lipid-binding proteins to regulate the clearance of cell corpses and other cell debris. However, it is unclear whether PtdSer and PtdEth contribute in similar or distinct ways to these processes. We discovered that disruption of the lipid flippases that maintain PtdSer or PtdEth asymmetry in the plasma membrane have opposite effects on phagocytosis in Caenorhabditis elegans embryos. Constitutive PtdSer externalization caused by disruption of the major PtdSer flippase TAT-1 led to increased phagocytosis of cell debris, sometimes leading to two cells engulfing the same debris. In contrast, PtdEth externalization caused by depletion of the major PtdEth flippase TAT-5 or its activator PAD-1 disrupted phagocytosis. These data suggest that PtdSer and PtdEth externalization have opposite effects on phagocytosis. Furthermore, externalizing PtdEth is associated with increased extracellular vesicle release, and we present evidence that the extent of extracellular vesicle accumulation correlates with the extent of phagocytic defects. Thus, a general loss of lipid asymmetry can have opposing impacts through different lipid subtypes simultaneously exerting disparate effects. KW - phagocytosis KW - lipid asymmetry KW - flippase KW - phosphatidylserine KW - phosphatidylethanolamine KW - extracellular vesicle Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208771 SN - 2296-634X VL - 8 ER - TY - JOUR A1 - Kümmel, Reiner A1 - Lindenberger, Dietmar T1 - Energy in Growth Accounting and the Aggregation of Capital and Output JF - Biophysical Economics and Sustainability N2 - We review the physical aggregation of value added and capital in terms of work performance and information processing and its relation to the deflated monetary time series of output and capital. In growth accounting it complements the time series of labor and energy, measured in hours worked per year and kilowatt-hours consumed per year, respectively. This aggregation is the conceptual basis on which those energy-dependent production functions have been constructed that reproduce economic growth of major industrial countries in the 20th century with small residuals and output elasticities that are for energy much larger and for labor much smaller than the cost shares of these factors. Accounting for growth in such a way, which deviates from that of mainstream economics, may serve as a first step towards integrating the First and the Second Law of Thermodynamics into economics. KW - aggregation KW - cost-share theorem KW - economic growth KW - energy KW - entropy KW - output elasicities Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241135 VL - 5 ER - TY - JOUR A1 - Guggenberger, Konstanze Viktoria A1 - Bley, Thorsten Alexander T1 - Imaging in Vasculitis JF - Current Rheumatology Reports N2 - Purpose of Review: Vasculitides are characterized by mostly autoimmunologically induced inflammatory processes of vascularstructures. They have various clinical and radiologic appearances. Early diagnosis and reliable monitoring are indispensable foradequate therapy to prevent potentially serious complications. Imaging, in addition to laboratory tests and physical examination,constitutes a key component in assessing disease extent and activity. This review presents current standards and some typicalfindings in the context of imaging in vasculitis with particular attention to large vessel vasculitides. Recent Findings: Recently, imaging has gained importance in the management of vasculitis, especially regarding large vesselvasculitides (LVV). Recently, EULAR (European League Against Rheumatism) has launched its recommendations concerningthe diagnosis of LVVs. Imaging is recommended as the preferred complement to clinical examination. Color-coded duplexsonography is considered the first choice imaging test in suspected giant cell arteritis, and magnetic resonance imaging isconsidered the first choice in suspected Takayasu’sarteritis. Summary: Due to diversity of clinical and radiologic presentations, diagnosis and therapy monitoring of vasculitides mayconstitute a challenge. As a result of ongoing technological progress, a variety of non-invasive imaging modalities now playan elemental role in the interdisciplinary management of vasculitic diseases. KW - Vasculitis KW - Large vessel vasculitides (LVV) KW - Giant cell arteritis (GCA KW - Imaging KW - Magnetic resonance imaging(MRI) KW - EULAR guidelines Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232762 SN - 1523-3774 VL - 22 IS - 34 ER - TY - JOUR A1 - Isaias, Ioannis U. A1 - Brumberg, Joachim A1 - Pozzi, Nicoló G. A1 - Palmisano, Chiara A1 - Canessa, Andrea A1 - Marotta, Giogio A1 - Volkmann, Jens A1 - Pezzoli, Gianni T1 - Brain metabolic alterations herald falls in patients with Parkinson's disease JF - Annals of Clinical and Translational Neurology N2 - Pathophysiological understanding of gait and balance disorders in Parkinson’s disease is insufficient and late recognition of fall risk limits efficacious followup to prevent or delay falls. We show a distinctive reduction of glucose metabolism in the left posterior parietal cortex, with increased metabolic activity in the cerebellum, in parkinsonian patients 6–8 months before their first fall episode. Falls in Parkinson’s disease may arise from altered cortical processing of body spatial orientation, possibly predicted by abnormal cortical metabolism. KW - Parkionson's disease KW - brain metabolic alterations Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235982 VL - 7 IS - 4 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Petritsch, Bernhard A1 - Buck, Andreas K. A1 - Serfling, Sebastian E. T1 - Pitfalls in PSMA-PET/CT: Intensive bone-marrow uptake in a case with polycythaemia vera JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - No abstract available. KW - bone-marrow Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235608 SN - 1619-7070 VL - 48 ER - TY - JOUR A1 - van Loock, Peter A1 - Alt, Wolfgang A1 - Becher, Christoph A1 - Benson, Oliver A1 - Boche, Holger A1 - Deppe, Christian A1 - Eschner, Jürgen A1 - Höfling, Sven A1 - Meschede, Dieter A1 - Michler, Peter A1 - Schmidt, Frank A1 - Weinfurter, Harald T1 - Extending Quantum Links: Modules for Fiber‐ and Memory‐Based Quantum Repeaters JF - Advanced Quantum Technologies N2 - Elementary building blocks for quantum repeaters based on fiber channels and memory stations are analyzed. Implementations are considered for three different physical platforms, for which suitable components are available: quantum dots, trapped atoms and ions, and color centers in diamond. The performances of basic quantum repeater links for these platforms are evaluated and compared, both for present‐day, state‐of‐the‐art experimental parameters as well as for parameters that can in principle be reached in the future. The ultimate goal is to experimentally explore regimes at intermediate distances—up to a few 100 km—in which the repeater‐assisted secret key transmission rates exceed the maximal rate achievable via direct transmission. Two different protocols are considered, one of which is better adapted to the higher source clock rate and lower memory coherence time of the quantum dot platform, while the other circumvents the need of writing photonic quantum states into the memories in a heralded, nondestructive fashion. The elementary building blocks and protocols can be connected in a modular form to construct a quantum repeater system that is potentially scalable to large distances. KW - color centers KW - quantum communication KW - quantum dots KW - quantum repeaters KW - trapped atoms/ions Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228322 VL - 3 IS - 11 ER - TY - JOUR A1 - Peixoto, Thiago R. F. A1 - Bentmann, Hendrik A1 - Rüßmann, Philipp A1 - Tcakaev, Abdul-Vakhab A1 - Winnerlein, Martin A1 - Schreyeck, Steffen A1 - Schatz, Sonja A1 - Vidal, Raphael Crespo A1 - Stier, Fabian A1 - Zabolotnyy, Volodymyr A1 - Green, Robert J. A1 - Min, Chul Hee A1 - Fornari, Celso I. A1 - Maaß, Henriette A1 - Vasili, Hari Babu A1 - Gargiani, Pierluigi A1 - Valvidares, Manuel A1 - Barla, Alessandro A1 - Buck, Jens A1 - Hoesch, Moritz A1 - Diekmann, Florian A1 - Rohlf, Sebastian A1 - Kalläne, Matthias A1 - Rossnagel, Kai A1 - Gould, Charles A1 - Brunner, Karl A1 - Blügel, Stefan A1 - Hinkov, Vladimir A1 - Molenkamp, Laurens W. A1 - Friedrich, Reinert T1 - Non-local effect of impurity states on the exchange coupling mechanism in magnetic topological insulators JF - NPJ Quantum Materials N2 - Since the discovery of the quantum anomalous Hall (QAH) effect in the magnetically doped topological insulators (MTI) Cr:(Bi,Sb)\(_2\)Te\(_3\) and V:(Bi,Sb)\(_2\)Te\(_3\), the search for the magnetic coupling mechanisms underlying the onset of ferromagnetism has been a central issue, and a variety of different scenarios have been put forward. By combining resonant photoemission, X-ray magnetic circular dichroism and density functional theory, we determine the local electronic and magnetic configurations of V and Cr impurities in (Bi,Sb)\(_2\)Te\(_3\). State-of-the-art first-principles calculations find pronounced differences in their 3d densities of states, and show how these impurity states mediate characteristic short-range pd exchange interactions, whose strength sensitively varies with the position of the 3d states relative to the Fermi level. Measurements on films with varying host stoichiometry support this trend. Our results explain, in an unified picture, the origins of the observed magnetic properties, and establish the essential role of impurity-state-mediated exchange interactions in the magnetism of MTI. KW - shape-truncation functions KW - semiconductors Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230686 VL - 5 ER - TY - JOUR A1 - Lock, J. F. A1 - Ungeheuer, L. A1 - Borst, P. A1 - Swol, J. A1 - Löb, S. A1 - Brede, E. M. A1 - Röder, D. A1 - Lengenfelder, B. A1 - Sauer, K. A1 - Gremer, C. - T. T1 - Markedly increased risk of postoperative bleeding complications during perioperative bridging anticoagulation in general and visceral surgery JF - Perioperative Medicine N2 - Background Increasing numbers of patients receiving oral anticoagulants are undergoing elective surgery. Low molecular weight heparin (LMWH) is frequently applied as bridging therapy during perioperative interruption of anticoagulation. The aim of this study was to explore the postoperative bleeding risk of patients receiving surgery under bridging anticoagulation. Methods We performed a monocentric retrospective two-arm matched cohort study. Patients that received perioperative bridging anticoagulation were compared to a matched control group with identical surgical procedure, age, and sex. Emergency and vascular operations were excluded. The primary endpoint was the incidence of major postoperative bleeding. Secondary endpoints were minor postoperative bleeding, thromboembolic events, length of stay, and in-hospital mortality. Multivariate analysis explored risk factors of major postoperative bleeding. Results A total of 263 patients in each study arm were analyzed. The patient cohort included the entire field of general and visceral surgery including a large proportion of major oncological resections. Bridging anticoagulation increased the postoperative incidence of major bleeding events (8% vs. 1%; p < 0.001) as well as minor bleeding events (14% vs. 5%; p < 0.001). Thromboembolic events were equally rare in both groups (1% vs. 2%; p = 0.45). No effect on mortality was observed (1.5% vs. 1.9%). Independent risk factors of major postoperative bleeding were full-therapeutic dose of LMWH, renal insufficiency, and the procedure-specific bleeding risk. Conclusion Perioperative bridging anticoagulation, especially full-therapeutic dose LMWH, markedly increases the risk of postoperative bleeding complications in general and visceral surgery. Surgeons should carefully consider the practice of routine bridging. KW - low molecular heparin KW - atrial fibrillation KW - postoperative bleeding KW - thromboembolism KW - anticoagulation KW - bridging KW - antithrombotic therapy KW - warfarin interruption KW - oral anticoagulants KW - management Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230690 VL - 9 ER - TY - JOUR A1 - Koessler, Juergen A1 - Klingler, Philipp A1 - Niklaus, Marius A1 - Weber, Katja A1 - Koessler, Angela A1 - Boeck, Markus A1 - Kobsar, Anna T1 - The Impact of Cold Storage on Adenosine Diphosphate-Mediated Platelet Responsiveness JF - TH Open N2 - Introduction  Cold storage of platelets is considered to contribute to lower risk of bacterial growth and to more efficient hemostatic capacity. For the optimization of storage strategies, it is required to further elucidate the influence of refrigeration on platelet integrity. This study focused on adenosine diphosphate (ADP)-related platelet responsiveness. Materials and Methods  Platelets were prepared from apheresis-derived platelet concentrates or from peripheral whole blood, stored either at room temperature or at 4°C. ADP-induced aggregation was tested with light transmission. Activation markers, purinergic receptor expression, and P2Y12 receptor function were determined by flow cytometry. P2Y1 and P2X1 function was assessed by fluorescence assays, cyclic nucleotide concentrations by immunoassays, and vasodilator-stimulated phosphoprotein (VASP)-phosphorylation levels by Western blot analysis. Results  In contrast to room temperature, ADP-induced aggregation was maintained under cold storage for 6 days, associated with elevated activation markers like fibrinogen binding or CD62P expression. Purinergic receptor expression was not essentially different, whereas P2Y1 function deteriorated rapidly at cold storage, but not P2Y12 activity. Inhibitory pathways of cold-stored platelets were characterized by reduced responses to nitric oxide and prostaglandin E1. Refrigeration of citrated whole blood also led to the attenuation of induced inhibition of platelet aggregation, detectable within 24 hours. Conclusion  ADP responsiveness is preserved under cold storage for 6 days due to stable P2Y12 activity and concomitant disintegration of inhibitory pathways enabling a higher reactivity of stored platelets. The ideal storage time at cold temperature for the highest hemostatic effect of platelets should be evaluated in further studies. KW - platelet physiology KW - cold storage KW - adenosine diphosphate KW - purinergic receptors KW - inhibitory signaling Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229387 VL - 4 IS - 3 ER - TY - JOUR A1 - Einsele, Hermann A1 - Borghaei, Hossein A1 - Orlowski, Robert Z. A1 - Subklewe, Marion A1 - Roboz, Gail J. A1 - Zugmaier, Gerhard A1 - Kufer, Peter A1 - Iskander, Karim A1 - Kantarjian, Hagop M. T1 - The BiTE (Bispecific T‐Cell Engager) Platform: Development and Future Potential of a Targeted Immuno‐Oncology Therapy Across Tumor Types JF - Cancer N2 - Immuno‐oncology therapies engage the immune system to treat cancer. BiTE (bispecific T‐cell engager) technology is a targeted immuno‐oncology platform that connects patients' own T cells to malignant cells. The modular nature of BiTE technology facilitates the generation of molecules against tumor‐specific antigens, allowing off‐the‐shelf immuno‐oncotherapy. Blinatumomab was the first approved canonical BiTE molecule and targets CD19 surface antigens on B cells, making blinatumomab largely independent of genetic alterations or intracellular escape mechanisms. Additional BiTE molecules in development target other hematologic malignancies (eg, multiple myeloma, acute myeloid leukemia, and B‐cell non‐Hodgkin lymphoma) and solid tumors (eg, prostate cancer, glioblastoma, gastric cancer, and small‐cell lung cancer). BiTE molecules with an extended half‐life relative to the canonical BiTE molecules are also being developed. Advances in immuno‐oncology made with BiTE technology could substantially improve the treatment of hematologic and solid tumors and offer enhanced activity in combination with other treatments. KW - B cell KW - blinatumomab KW - hematologic malignancies KW - T cell KW - tumor‐specific antigen Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215426 VL - 126 IS - 14 SP - 3192 EP - 3201 ER - TY - JOUR A1 - Capetian, Philipp A1 - Müller, Lorenz A1 - Volkmann, Jens A1 - Heckmann, Manfred A1 - Ergün, Süleyman A1 - Wagner, Nicole T1 - Visualizing the synaptic and cellular ultrastructure in neurons differentiated from human induced neural stem cells - an optimized protocol JF - International Journal of Molecular Sciences N2 - The size of the synaptic subcomponents falls below the limits of visible light microscopy. Despite new developments in advanced microscopy techniques, the resolution of transmission electron microscopy (TEM) remains unsurpassed. The requirements of tissue preservation are very high, and human post mortem material often does not offer adequate quality. However, new reprogramming techniques that generate human neurons in vitro provide samples that can easily fulfill these requirements. The objective of this study was to identify the culture technique with the best ultrastructural preservation in combination with the best embedding and contrasting technique for visualizing neuronal elements. Two induced neural stem cell lines derived from healthy control subjects underwent differentiation either adherent on glass coverslips, embedded in a droplet of highly concentrated Matrigel, or as a compact neurosphere. Afterward, they were fixed using a combination of glutaraldehyde (GA) and paraformaldehyde (PFA) followed by three approaches (standard stain, Ruthenium red stain, high contrast en-bloc stain) using different combinations of membrane enhancing and contrasting steps before ultrathin sectioning and imaging by TEM. The compact free-floating neurospheres exhibited the best ultrastructural preservation. High-contrast en-bloc stain offered particularly sharp staining of membrane structures and the highest quality visualization of neuronal structures. In conclusion, compact neurospheres growing under free-floating conditions in combination with a high contrast en-bloc staining protocol, offer the optimal preservation and contrast with a particular focus on visualizing membrane structures as required for analyzing synaptic structures. KW - transmission electron microscopy KW - human neurons KW - induced neural stem cells KW - synapse KW - synaptic vesicles KW - high contrast Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236053 SN - 1422-0067 VL - 21 IS - 5 ER - TY - JOUR A1 - Livingstone, E. A1 - Zaremba, A. A1 - Horn, S. A1 - Ugurel, S. A1 - Casalini, B. A1 - Schlaak, M. A1 - Hassel, J.C. A1 - Herbst, R. A1 - Utikal, J.S. A1 - Weide, B. A1 - Gutzmer, R. A1 - Meier, F. A1 - Koelsche, C. A1 - Hadaschik, E. A1 - Sucker, A. A1 - Reis, H. A1 - Merkelbach‐Bruse, S. A1 - Siewert, M. A1 - Sahm, F. A1 - von Deimling, A. A1 - Cosgarea, I. A1 - Zimmer, L. A1 - Schadendorf, D. A1 - Schilling, B. A1 - Griewank, K.G. T1 - GNAQ and GNA11 mutant nonuveal melanoma: a subtype distinct from both cutaneous and uveal melanoma JF - British Journal of Dermatology N2 - Background GNAQ and GNA11 mutant nonuveal melanoma represent a poorly characterized rare subgroup of melanoma with a gene mutation profile similar to uveal melanoma. Objectives To characterize these tumours in terms of clinical behaviour and genetic characteristics. Methods Patients with nonuveal GNAQ/11 mutated melanoma were identified from the prospective multicentre tumour tissue registry ADOREG, Tissue Registry in Melanoma (TRIM) and additional cooperating skin cancer centres. Extensive data on patient, tumour and treatment characteristics were collected retrospectively. Targeted sequencing was used to determine tumour mutational burden. Immunohistochemistry staining was performed for programmed death‐ligand 1 and BRCA1‐associated protein (BAP)1. Existing whole‐exome cutaneous and uveal melanoma data were analysed for mutation type and burden. Results We identified 18 patients with metastatic GNAQ/11 mutant nonuveal melanoma. Tumours had a lower tumour mutational burden and fewer ultraviolet signature mutations than cutaneous melanomas. In addition to GNAQ and GNA11 mutations (nine each), six splicing factor 3b subunit 1 (SF3B1), three eukaryotic translation initiation factor 1A X‐linked (EIF1AX) and four BAP1 mutations were detected. In contrast to uveal melanoma, GNAQ/11 mutant nonuveal melanomas frequently metastasized lymphatically and concurrent EIF1AX, SF3B1 and BAP1 mutations showed no apparent association with patient prognosis. Objective response to immunotherapy was poor with only one partial response observed in 10 treated patients (10%). Conclusions Our findings suggest that GNAQ/11 mutant nonuveal melanomas are a subtype of melanoma that is both clinically and genetically distinct from cutaneous and uveal melanoma. As they respond poorly to available treatment regimens, novel effective therapeutic approaches for affected patients are urgently needed. What is already known about this topic? The rare occurrence of GNAQ/11 mutations in nonuveal melanoma has been documented. GNAQ/11 mutant nonuveal melanomas also harbour genetic alterations in EIF1AX, SF3B1 and BAP1 that are of prognostic relevance in uveal melanoma. What does this study add? GNAQ/11 mutant nonuveal melanomas show metastatic spread reminiscent of cutaneous melanoma, but not uveal melanoma. GNAQ/11 mutant nonuveal melanomas have a low tumour mutational burden that is higher than uveal melanoma, but lower than cutaneous melanoma. What is the translational message? Primary GNAQ/11 mutant nonuveal melanomas are a subtype of melanoma that is clinically and genetically distinct from both cutaneous and uveal melanoma. As metastatic GNAQ/11 mutant nonuveal melanomas respond poorly to available systemic therapies, including immune checkpoint inhibition, novel therapeutic approaches for these tumours are urgently needed. KW - melanoma KW - GNAQ KW - GNA11 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215434 VL - 183 IS - 5 SP - 928 EP - 939 ER - TY - JOUR A1 - Weißbach, Susann A1 - Heredia-Guerrero, Sofia Catalina A1 - Barnsteiner, Stefanie A1 - Großhans, Lukas A1 - Bodem, Jochen A1 - Starz, Hanna A1 - Langer, Christian A1 - Appenzeller, Silke A1 - Knop, Stefan A1 - Steinbrunn, Torsten A1 - Rost, Simone A1 - Einsele, Hermann A1 - Bargou, Ralf Christian A1 - Rosenwald, Andreas A1 - Stühmer, Thorsten A1 - Leich, Ellen T1 - Exon-4 Mutations in KRAS Affect MEK/ERK and PI3K/AKT Signaling in Human Multiple Myeloma Cell Lines JF - Cancers N2 - Approximately 20% of multiple myeloma (MM) cases harbor a point mutation in KRAS. However, there is still no final consent on whether KRAS-mutations are associated with disease outcome. Specifically, no data exist on whether KRAS-mutations have an impact on survival of MM patients at diagnosis in the era of novel agents. Direct blockade of KRAS for therapeutic purposes is mostly impossible, but recently a mutation-specific covalent inhibitor targeting KRAS\(^{p.G12C}\) entered into clinical trials. However, other KRAS hotspot-mutations exist in MM patients, including the less common exon-4 mutations. For the current study, the coding regions of KRAS were deep-sequenced in 80 newly diagnosed MM patients, uniformely treated with three cycles of bortezomib plus dexamethasone and cyclophosphamide (VCD)-induction, followed by high-dose chemotherapy and autologous stem cell transplantation. Moreover, the functional impact of KRAS\(^{p.G12A}\) and the exon-4 mutations p.A146T and p.A146V on different survival pathways was investigated. Specifically, KRAS\(^{WT}\), KRAS\(^{p.G12A}\), KRAS\(^{p.A146T}\), and KRAS\(^{p.A146V}\) were overexpressed in HEK293 cells and the KRAS\(^{WT}\) MM cell lines JJN3 and OPM2 using lentiviral transduction and the Sleeping Beauty vector system. Even though KRAS-mutations were not correlated with survival, all KRAS-mutants were found capable of potentially activating MEK/ERK- and sustaining PI3K/AKT-signaling in MM cells. KW - multiple myeloma KW - KRAS KW - MEK/ERK-signaling KW - AKT-signaling KW - amplicon sequencing Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200617 SN - 2072-6694 VL - 12 IS - 2 ER - TY - JOUR A1 - Metzenmacher, Martin A1 - Váraljai, Renáta A1 - Hegedüs, Balazs A1 - Cima, Igor A1 - Forster, Jan A1 - Schramm, Alexander A1 - Scheffler, Björn A1 - Horn, Peter A. A1 - Klein, Christoph A. A1 - Szarvas, Tibor A1 - Reis, Hennig A1 - Bielefeld, Nicola A1 - Roesch, Alexander A1 - Aigner, Clemens A1 - Kunzmann, Volker A1 - Wiesweg, Marcel A1 - Siveke, Jens T. A1 - Schuler, Martin A1 - Lueong, Smiths S. T1 - Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer JF - Cancers N2 - Early detection of cancer holds high promise for reducing cancer-related mortality. Detection of circulating tumor-specific nucleic acids holds promise, but sensitivity and specificity issues remain with current technology. We studied cell-free RNA (cfRNA) in patients with non-small cell lung cancer (NSCLC; n = 56 stage IV, n = 39 stages I-III), pancreatic cancer (PDAC, n = 20 stage III), malignant melanoma (MM, n = 12 stage III-IV), urothelial bladder cancer (UBC, n = 22 stage II and IV), and 65 healthy controls by means of next generation sequencing (NGS) and real-time droplet digital PCR (RT-ddPCR). We identified 192 overlapping upregulated transcripts in NSCLC and PDAC by NGS, more than 90% of which were noncoding. Previously reported transcripts (e.g., HOTAIRM1) were identified. Plasma cfRNA transcript levels of POU6F2-AS2 discriminated NSCLC from healthy donors (AUC = 0.82 and 0.76 for stages IV and I–III, respectively) and significantly associated (p = 0.017) with the established tumor marker Cyfra 21-1. cfRNA yield and POU6F2-AS transcript abundance discriminated PDAC patients from healthy donors (AUC = 1.0). POU6F2-AS2 transcript was significantly higher in MM (p = 0.044). In summary, our findings support further validation of cfRNA detection by RT-ddPCR as a biomarker for early detection of solid cancers. KW - liquid biopsy KW - cfRNA KW - cancer KW - ddPCR KW - NGS KW - POU6F2-AS2 KW - early detection Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200553 SN - 2072-6694 VL - 12 IS - 2 ER - TY - JOUR A1 - Christian, Gentzsch A1 - Seier, Kerstin A1 - Drakopoulos, Antonios A1 - Jobin, Marie-Lise A1 - Lanoiselée, Yann A1 - Koszegi, Zsombor A1 - Maurel, Damien A1 - Sounier, Rémy A1 - Hübner, Harald A1 - Gmeiner, Peter A1 - Granier, Sébastien A1 - Calebiro, Davide A1 - Decker, Michael T1 - Selective and Wash‐Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single‐Molecule Imaging of μ‐Opioid Receptor Dimerization JF - Angewandte Chemie International Edition N2 - μ‐Opioid receptors (μ‐ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ‐ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ‐OR antagonist E‐p‐nitrocinnamoylamino‐dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity. Using these ligands, we achieved single‐molecule imaging of μ‐ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of μ‐ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that μ‐ORs interact with each other to form short‐lived homodimers on the plasma membrane. This approach provides a new strategy to investigate μ‐OR pharmacology at single‐molecule level. KW - single-molecule microscopy KW - fluorescent probes KW - G-protein coupled receptor KW - homodimerization KW - opioid ligands Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212398 VL - 59 IS - 15 ER - TY - BOOK A1 - Guth, Denis T1 - Zur Sicherstellung der ‚Verträglichkeit‘ innerstädtischer Einkaufszentren - Raumbezogene Diskurs- und Kalkulationsordnungen am Beispiel der Mainzer Innenstadt N2 - Der Begriff der ‚Verträglichkeit‘ spielt eine zentrale Rolle für die politisch-planerische Steuerung von Einzelhandels- und Stadtentwicklung. Besonders kontrovers wird v.a. seit Mitte der 1990er Jahre die Frage der ‚Verträglichkeit‘ innerstädtischer Einkaufszentren diskutiert. Die vorliegende Studie untersucht anhand ehemaliger Shopping-Center-Planungen für die Mainzer Innenstadt, wie der Verträglichkeitsbegriff in der Praxis gefüllt wird und welche planerischen Steuerungslogiken hieraus hervorgehen. Die Arbeit setzt sich kritisch mit der Frage auseinander, auf welche normativen Wissensordnungen über den innerstädtischen Raum sich die politisch-planerische Bearbeitung der Verträglichkeitsproblematik stützt und welche Machtwirkungen hiermit einhergehen. Ausgehend von einer poststrukturalistisch inspirierten, diskurstheoretischen Perspektive verschiebt die Studie damit den geographischen Blick auf die Verträglichkeitsfrage: Was ‚Verträglichkeit‘ für die politisch-planerische Praxis konkret bedeutet, ob ein geplantes Einkaufszentrum als ‚(innenstadt)verträglich‘ gelten kann bzw. welche konkreten Interventionen dies erfordert, hängt demzufolge weniger von objektiven ökonomischen, räumlichen oder städtebaulichen Gegebenheiten ab – vielmehr zeigt die Studie, dass eine ganzen Reihe von Techniken raumbezogener Wissensproduktion mobilisiert werden müssen, damit die Verträglichkeitsfrage überhaupt als eine objektivierbare Frage erscheinen kann. T3 - Geographische Handelsforschung - 29 KW - Einkaufszentrum KW - Diskurs KW - Diskurs KW - Einkaufszentrum KW - Mainz KW - Innenstadt Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-192670 SN - 978-3-95826-130-3 SN - 978-3-95826-131-0 N1 - Parallel erschienen als Druckausgabe in Würzburg University Press, 978-3-95826-130-3, 29,80 Euro. PB - Würzburg University Press CY - Würzburg ER - TY - JOUR A1 - Feireisl, Eduard A1 - Klingenberg, Christian A1 - Markfelder, Simon T1 - On the density of “wild” initial data for the compressible Euler system JF - Calculus of Variations and Partial Differential Equations N2 - We consider a class of “wild” initial data to the compressible Euler system that give rise to infinitely many admissible weak solutions via the method of convex integration. We identify the closure of this class in the natural L1-topology and show that its complement is rather large, specifically it is an open dense set. KW - Euler system Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232607 SN - 0944-2669 VL - 59 ER - TY - JOUR A1 - Reinermann, Sophie A1 - Asam, Sarah A1 - Kuenzer, Claudia T1 - Remote Sensing of Grassland Production and Management - A Review JF - Remote Sensing N2 - Grasslands cover one third of the earth’s terrestrial surface and are mainly used for livestock production. The usage type, use intensity and condition of grasslands are often unclear. Remote sensing enables the analysis of grassland production and management on large spatial scales and with high temporal resolution. Despite growing numbers of studies in the field, remote sensing applications in grassland biomes are underrepresented in literature and less streamlined compared to other vegetation types. By reviewing articles within research on satellite-based remote sensing of grassland production traits and management, we describe and evaluate methods and results and reveal spatial and temporal patterns of existing work. In addition, we highlight research gaps and suggest research opportunities. The focus is on managed grasslands and pastures and special emphasize is given to the assessment of studies on grazing intensity and mowing detection based on earth observation data. Grazing and mowing highly influence the production and ecology of grassland and are major grassland management types. In total, 253 research articles were reviewed. The majority of these studies focused on grassland production traits and only 80 articles were about grassland management and use intensity. While the remote sensing-based analysis of grassland production heavily relied on empirical relationships between ground-truth and satellite data or radiation transfer models, the used methods to detect and investigate grassland management differed. In addition, this review identified that studies on grassland production traits with satellite data often lacked including spatial management information into the analyses. Studies focusing on grassland management and use intensity mostly investigated rather small study areas with homogeneous intensity levels among the grassland parcels. Combining grassland production estimations with management information, while accounting for the variability among grasslands, is recommended to facilitate the development of large-scale continuous monitoring and remote sensing grassland products, which have been rare thus far. KW - pasture KW - use intensity KW - grazing KW - mowing KW - productivity KW - biomass KW - yield KW - satellite data KW - optical KW - SAR Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207799 SN - 2072-4292 VL - 12 IS - 12 ER - TY - JOUR A1 - Dhillon, Maninder Singh A1 - Dahms, Thorsten A1 - Kuebert-Flock, Carina A1 - Borg, Erik A1 - Conrad, Christopher A1 - Ullmann, Tobias T1 - Modelling Crop Biomass from Synthetic Remote Sensing Time Series: Example for the DEMMIN Test Site, Germany JF - Remote Sensing N2 - This study compares the performance of the five widely used crop growth models (CGMs): World Food Studies (WOFOST), Coalition for Environmentally Responsible Economies (CERES)-Wheat, AquaCrop, cropping systems simulation model (CropSyst), and the semi-empiric light use efficiency approach (LUE) for the prediction of winter wheat biomass on the Durable Environmental Multidisciplinary Monitoring Information Network (DEMMIN) test site, Germany. The study focuses on the use of remote sensing (RS) data, acquired in 2015, in CGMs, as they offer spatial information on the actual conditions of the vegetation. Along with this, the study investigates the data fusion of Landsat (30 m) and Moderate Resolution Imaging Spectroradiometer (MODIS) (500 m) data using the spatial and temporal reflectance adaptive reflectance fusion model (STARFM) fusion algorithm. These synthetic RS data offer a 30-m spatial and one-day temporal resolution. The dataset therefore provides the necessary information to run CGMs and it is possible to examine the fine-scale spatial and temporal changes in crop phenology for specific fields, or sub sections of them, and to monitor crop growth daily, considering the impact of daily climate variability. The analysis includes a detailed comparison of the simulated and measured crop biomass. The modelled crop biomass using synthetic RS data is compared to the model outputs using the original MODIS time series as well. On comparison with the MODIS product, the study finds the performance of CGMs more reliable, precise, and significant with synthetic time series. Using synthetic RS data, the models AquaCrop and LUE, in contrast to other models, simulate the winter wheat biomass best, with an output of high R2 (>0.82), low RMSE (<600 g/m\(^2\)) and significant p-value (<0.05) during the study period. However, inputting MODIS data makes the models underperform, with low R2 (<0.68) and high RMSE (>600 g/m\(^2\)). The study shows that the models requiring fewer input parameters (AquaCrop and LUE) to simulate crop biomass are highly applicable and precise. At the same time, they are easier to implement than models, which need more input parameters (WOFOST and CERES-Wheat). KW - crop growth models KW - Landsat KW - MODIS KW - data fusion KW - STARFM KW - climate parameters KW - winter wheat Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207845 SN - 2072-4292 VL - 12 IS - 11 ER - TY - JOUR A1 - Mitra, Sourav T1 - Local Existence of Strong Solutions of a Fluid–Structure Interaction Model JF - Journal of Mathematical Fluid Mechanics N2 - We are interested in studying a system coupling the compressible Navier–Stokes equations with an elastic structure located at the boundary of the fluid domain. Initially the fluid domain is rectangular and the beam is located on the upper side of the rectangle. The elastic structure is modeled by an Euler–Bernoulli damped beam equation. We prove the local in time existence of strong solutions for that coupled system. KW - fluid–structure interaction model KW - compressible fluid KW - Euler–Bernoulli damped beam KW - local existence Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235097 SN - 1422-6928 VL - 22 ER - TY - JOUR A1 - Schönlein, Michael T1 - Ensemble reachability of homogenous parameter‐depedent systems JF - Proceedings in Applied Mathematics and Mechanics N2 - In this paper we consider the class (θA, B) of parameter-dependent linear systems given by matrices A ∈ ℂ\(^{nxn}\) and B ∈ ℂ\(^{nxm}\). This class is of interest for several applications and the frequently met task for such systems is to steer the origin toward a given target family f(θ) by using an input that is independent from the parameter. This paper provides a collection of necessary and sufficient conditions for ensemble reachability for these systems. KW - ensemble reachability KW - homogenous parameter-depedent systems KW - mathematics Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257637 VL - 20 IS - 1 ER - TY - JOUR A1 - Herrmann, Thomas A1 - Fichtner, Alina Suzann A1 - Karunakaran, Mohindar Murugesh T1 - An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells JF - Cells N2 - About 1–5% of human blood T cells are Vγ9Vδ2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains contain a rearrangement of Vγ9 with JP (TRGV9JP or Vγ2Jγ1.2) and are paired with Vδ2 (TRDV2)-containing δ-chains. These TCRs respond to phosphoantigens (PAg) such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is found in many pathogens, and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. Until recently, these cells were believed to be restricted to primates, while no such cells are found in rodents. The identification of three genes pivotal for PAg recognition encoding for Vγ9, Vδ2, and butyrophilin (BTN) 3 in various non-primate species identified candidate species possessing PAg-reactive Vγ9Vδ2 T cells. Here, we review the current knowledge of the molecular basis of PAg recognition. This not only includes human Vγ9Vδ2 T cells and the recent discovery of BTN2A1 as Vγ9-binding protein mandatory for the PAg response but also insights gained from the identification of functional PAg-reactive Vγ9Vδ2 T cells and BTN3 in the alpaca and phylogenetic comparisons. Finally, we discuss models of the molecular basis of PAg recognition and implications for the development of transgenic mouse models for PAg-reactive Vγ9Vδ2 T cells. KW - γδ T cell KW - phosphoantigen KW - BTN KW - butyrophilin 3 KW - butyrophilin 2A1 KW - evolution KW - alpaca KW - human Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207937 SN - 2073-4409 VL - 9 IS - 6 ER - TY - JOUR A1 - Ban, Željka A1 - Griesbeck, Stefanie A1 - Tomić, Sanja A1 - Nitsch, Jörn A1 - Marder, Todd B. A1 - Piantanida, Ivo T1 - A Quadrupolar Bis-Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins JF - Chemistry - A European Journal N2 - A water‐soluble tetracationic quadrupolar bis‐triarylborane chromophore showed strong binding to ds‐DNA, ds‐RNA, ss‐RNA, as well as to the naturally most abundant protein, BSA. The novel dye can distinguish between DNA/RNA and BSA by fluorescence emission separated by Δv =3600 cm\(^{-1}\), allowing for the simultaneous quantification of DNA/RNA and protein (BSA) in a mixture. The applicability of such fluorimetric differentiation in vitro was demonstrated, strongly supporting a protein‐like target as a dominant binding site of 1 in cells. Moreover, our dye also bound strongly to ss‐RNA, with the unusual rod‐like structure of the dye, decorated by four positive charges at its termini and having a hydrophobic core, acting as a spindle for wrapping A, C and U ss‐RNAs, but not poly G, the latter preserving its secondary structure. To the best of our knowledge, such unmatched, multifaceted binding activity of a small molecule toward DNA, RNA, and proteins and the selectivity of its fluorimetric and chirooptic response makes the quadrupolar bis‐triarylborane a novel chromophore/fluorophore moiety for biochemical applications. KW - boranes KW - circular dichrosism KW - fluorescent probes KW - luminescence KW - sensors Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208154 VL - 26 IS - 10 ER - TY - JOUR A1 - Liu, Xiaocui A1 - Ming, Wenbo A1 - Friedrich, Alexandra A1 - Kerner, Florian A1 - Marder, Todd B. T1 - Copper-Catalyzed Triboration of Terminal Alkynes Using B\(_2\)pin\(_2\): Efficient Synthesis of 1,1,2-Triborylalkenes JF - Angewandte Chemie International Edition N2 - We report herein the catalytic triboration of terminal alkynes with B\(_2\)pin\(_2\) (bis(pinacolato)diboron) using readily available Cu(OAc)\(_2\) and P\(^n\)Bu\(_3\). Various 1,1,2‐triborylalkenes, a class of compounds that have been demonstrated to be potential matrix metalloproteinase (MMP‐2) inhibitors, were obtained directly in moderate to good yields. The process features mild reaction conditions, a broad substrate scope, and good functional group tolerance. This copper‐catalyzed reaction can be conducted on a gram scale to produce the corresponding 1,1,2‐triborylalkenes in modest yields. The utility of these products was demonstrated by further transformations of the C−B bonds to prepare gem ‐dihaloborylalkenes (F, Cl, Br), monohaloborylalkenes (Cl, Br), and trans ‐diaryldiborylalkenes, which serve as important synthons and have previously been challenging to prepare. KW - boronate esters KW - borylation KW - cross-coupling KW - diboration KW - halogenation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206694 VL - 59 IS - 1 ER - TY - JOUR A1 - Bohnert, Simone A1 - Seiffert, Anja A1 - Trella, Stefanie A1 - Bohnert, Michael A1 - Distel, Luitpold A1 - Ondruschka, Benjamin A1 - Monoranu, Camelia-Marie T1 - TMEM119 as a specific marker of microglia reaction in traumatic brain injury in postmortem examination JF - International Journal of Legal Medicine N2 - The aim of the present study was a refined analysis of neuroinflammation including TMEM119 as a useful microglia-specific marker in forensic assessments of traumatic causes of death, e.g., traumatic brain injury (TBI). Human brain tissue samples were obtained from autopsies and divided into cases with lethal TBI (n = 25) and subdivided into three groups according to their trauma survival time and compared with an age-, gender-, and postmortem interval-matched cohort of sudden cardiovascular fatalities as controls (n = 23). Brain tissue samples next to cortex contusions and surrounding white matter as well as samples of the ipsilateral uninjured brain stem and cerebellum were collected and stained immunohistochemically with antibodies against TMEM119, CD206, and CCR2. We could document the highest number of TMEM119-positive cells in acute TBI death with highly significant differences to the control numbers. CCR2-positive monocytes showed a significantly higher cell count in the cortex samples of TBI cases than in the controls with an increasing number of immunopositive cells over time. The number of CD206-positive M2 microglial cells increased survival time-dependent. After 3 days of survival, the cell number increased significantly in all four regions investigated compared with controls. In sum, we validate a specific and robustly expressed as well as fast reacting microglia marker, TMEM119, which distinguishes microglia from resident and infiltrating macrophages and thus offers a great potential for the estimation of the minimum survival time after TBI. KW - cerebrospinal fluid KW - forensic neuropathology KW - forensic neurotraumatology KW - immunohistochemistry KW - biomarker Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235346 SN - 0937-9827 VL - 134 ER - TY - JOUR A1 - Jellinghaus, K. A1 - Matin, S. A1 - Urban, P. A1 - Bohnert, M. A1 - Jantz, R. T1 - Study of the K-S distance on skulls from different modern populations for sex and ancestry determination JF - Rechtsmedizin N2 - In forensic science determination of the origin and sex of skeletal remains is an important task for identification purposes. In this study we investigated the krotaphion-sphenion distance (K‑S distance) in the pterion region of German, Euro-American, African-American and Rwandan skulls of modern individuals from the nineteenth to the twenty-first century to look for statistically significant differences in sex and ancestry. We found a statistically significant sex-specific difference in the K‑S distance, which was greater in male skulls than in female skulls for both sides of the skull. Our study also showed that there is a statistically significant difference in the K‑S distance between the four populations studied. Landmarks and morphometric parameters measured in our investigations, which were not used for the present examination were provided to the software program Fordisc for its reference data to enhance the range of its usability for identification of unknown skulls or partial skulls of European individuals. N2 - Bei der forensischen Begutachtung zur Identifizierung unbekannter Skelettfunde spielen Herkunftsanlaysen und Geschlechtsbestimmungen eine bedeutende Rolle. In unserer Studie an euroamerikanischen, afroamerikanischen, ruandischen und deutschen Schädeln untersuchte unsere Arbeitsgruppe die sog. Krotaphion-Sphenion-Distanz in der Pterion Region am menschlichen Schädel, um geschlechts- und herkunftsspezifische Unterschiede näher zu beleuchten. Unsere Ergebnisse zeigen einen signifikanten Unterschied in der K‑S-Distanz: Männliche Individuen zeigten auf beiden Seiten des Schädels signifikant größere Werte als weibliche Individuen, des Weiteren waren signifikante Unterschiede unter den vier untersuchten Populationen festzustellen. Die weiteren, im Rahmen der Studie gemessenen, jedoch für die vorliegende Auswertung nicht verwendeten Landmarken und morphometrischen Parameter der Schädel gingen in die Datenbank für die Identifizierungs-Software Fordisc ein, um deren Datengrundlage und damit Nutzbarkeit zur Identifikation unbekannter Schädel oder Schädelteile europäischer Individuen zu verbessern. KW - forensic anthropology KW - forensic osteology KW - identification KW - gender KW - landmarks KW - Forensische Anthropologie KW - Forensische Osteologie KW - Identifizierung KW - Geschlechtsbestimmung KW - Landmarken Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235185 SN - 0937-9819 VL - 30 ER - TY - JOUR A1 - Ziegler, Georg C. A1 - Almos, Peter A1 - McNeill, Rhiannon V. A1 - Jansch, Charline A1 - Lesch, Klaus‐Peter T1 - Cellular effects and clinical implications of SLC2A3 copy number variation JF - Journal of Cellular Physiology N2 - SLC2A3 encodes the predominantly neuronal glucose transporter 3 (GLUT3), which facilitates diffusion of glucose across plasma membranes. The human brain depends on a steady glucose supply for ATP generation, which consequently fuels critical biochemical processes, such as axonal transport and neurotransmitter release. Besides its role in the central nervous system, GLUT3 is also expressed in nonneural organs, such as the heart and white blood cells, where it is equally involved in energy metabolism. In cancer cells, GLUT3 overexpression contributes to the Warburg effect by answering the cell's increased glycolytic demands. The SLC2A3 gene locus at chromosome 12p13.31 is unstable and prone to non‐allelic homologous recombination events, generating multiple copy number variants (CNVs) of SLC2A3 which account for alterations in SLC2A3 expression. Recent associations of SLC2A3 CNVs with different clinical phenotypes warrant investigation of the potential influence of these structural variants on pathomechanisms of neuropsychiatric, cardiovascular, and immune diseases. In this review, we accumulate and discuss the evidence how SLC2A3 gene dosage may exert diverse protective or detrimental effects depending on the pathological condition. Cellular states which lead to increased energetic demand, such as organ development, proliferation, and cellular degeneration, appear particularly susceptible to alterations in SLC2A3 copy number. We conclude that better understanding of the impact of SLC2A3 variation on disease etiology may potentially provide novel therapeutic approaches specifically targeting this GLUT. KW - copy number variation KW - energy metabolism KW - glucose transporter KW - GLUT3 KW - neurodegeneration KW - neurodevelopment KW - SLC2A3 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218009 VL - 235 IS - 12 SP - 9021 EP - 9036 ER - TY - JOUR A1 - Dietschreit, Johannes C. B. A1 - Wagner, Annika A1 - Le, T. Anh A1 - Klein, Philipp A1 - Schindelin, Hermann A1 - Opatz, Till A1 - Engels, Bernd A1 - Hellmich, Ute A. A1 - Ochsenfeld, Christian T1 - Predicting \(^{19}\)F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex JF - Angewandte Chemie International Edition N2 - The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable \(^{19}\)F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the \(^{19}\)F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein–inhibitor conformations as well as monomeric and dimeric inhibitor–protein complexes, thus rendering it the largest computational study on chemical shifts of \(^{19}\)F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area. KW - African sleeping sickness KW - covalent inhibitors KW - NMR spectroscopy KW - quantum chemistry KW - structural biology Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214879 VL - 59 IS - 31 SP - 12669 EP - 12673 ER - TY - JOUR A1 - Ameri, Pietro A1 - Schiattarella, Gabriele Giacomo A1 - Crotti, Lia A1 - Torchio, Margherita A1 - Bertero, Edoardo A1 - Rodolico, Daniele A1 - Forte, Maurizio A1 - Di Mauro, Vittoria A1 - Paolillo, Roberta A1 - Chimenti, Cristina A1 - Torella, Daniele A1 - Catalucci, Daniele A1 - Sciarretta, Sebastiano A1 - Basso, Cristina A1 - Indolfi, Ciro A1 - Perrino, Cinzia T1 - Novel basic science insights to improve the management of heart failure: Review of the working group on cellular and molecular biology of the heart of the Italian Society of Cardiology JF - International Journal of Molecular Sciences N2 - Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding novel treatments. Here, we discuss recent basic science insights that encompass major areas of translational research in HF and have high potential clinical impact. KW - heart failure KW - basic KW - translational KW - research KW - mechanisms Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285085 SN - 1422-0067 VL - 21 IS - 4 ER - TY - JOUR A1 - Wirth, Robert A1 - Foerster, Anna A1 - Kunde, Wilfried A1 - Pfister, Roland T1 - Design choices: Empirical recommendations for designing two-dimensional finger-tracking experiments JF - Behavior Research Methods N2 - The continuous tracking of mouse or finger movements has become an increasingly popular research method for investigating cognitive and motivational processes such as decision-making, action-planning, and executive functions. In the present paper, we evaluate and discuss how apparently trivial design choices of researchers may impact participants’ behavior and, consequently, a study’s results. We first provide a thorough comparison of mouse- and finger-tracking setups on the basis of a Simon task. We then vary a comprehensive set of design factors, including spatial layout, movement extent, time of stimulus onset, size of the target areas, and hit detection in a finger-tracking variant of this task. We explore the impact of these variations on a broad spectrum of movement parameters that are typically used to describe movement trajectories. Based on our findings, we suggest several recommendations for best practice that avoid some of the pitfalls of the methodology. Keeping these recommendations in mind will allow for informed decisions when planning and conducting future tracking experiments. KW - movement tracking KW - experimental design KW - Simon task KW - measures Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235569 VL - 52 ER - TY - JOUR A1 - Roth, Nicolas A1 - Zoder, Sebastian A1 - Zaman, Assad Ali A1 - Thorn, Simon A1 - Schmidl, Jürgen T1 - Long‐term monitoring reveals decreasing water beetle diversity, loss of specialists and community shifts over the past 28 years JF - Insect Conservation and Diversity N2 - Lentic freshwater organisms are influenced by a multitude of factors, including geomorphology, hydrology, anthropogenic impacts and climate change. Organisms that depend on patchy resources such as water beetles may also be sensitive to anthropogenic habitat degradation, like pollution, eutrophication, water level or management alteration. To assess composition and ecological trends in the water beetle communities of Central Europe, we sampled water beetles (Dytiscidae, Haliplidae, Noteridae) in 33 water bodies in Southern Germany from 1991 to 2018. We used manual, time‐standardised capture during three periods: between 1991 and 1995, 2007 and 2008, and 2017 and 2018. During the 28‐year survey period, we captured a total of 81 species. We found annual declines in both species number (ca −1%) and abundance (ca −2%). Also, community composition showed significant changes over time. The significant impact of pH on the community composition suggests that the recorded changes through time partly reflect natural succession processes. However, a pronounced decline of beetle species belonging to the moor‐related beetle associations indicated that Central European water beetles are also threatened by non‐successional factors, including desiccation, increased nitrogen input and/or mineralisation, and the loss of specific habitats. This trend to physiographical homogenisation resulted in corresponding community composition shifts. To effectively protect endangered species, conservation strategies need to be aimed at regularly creating new water bodies with mineralic bottom substratum, and maintenance of moor water bodies that represent late successional stages. KW - biodiversity KW - lentic inland water bodies KW - long‐term monitoring KW - time series KW - water beetles Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214905 VL - 13 IS - 2 SP - 140 EP - 150 ER - TY - JOUR A1 - Susewind, Moritz A1 - Walkowitz, Gari T1 - Symbolic Moral Self-Completion – Social Recognition of Prosocial Behavior Reduces Subsequent Moral Striving JF - Frontiers in Psychology N2 - According to theories on moral balancing, a prosocial act can decrease people’s motivation to engage in subsequent prosocial behavior, because people feel that they have already achieved a positive moral self-perception. However, there is also empirical evidence showing that people actually need to be recognized by others in order to establish and affirm their self-perception through their prosocial actions. Without social recognition, moral balancing could possibly fail. In this paper, we investigate in two laboratory experiments how social recognition of prosocial behavior influences subsequent moral striving. Building on self-completion theory, we hypothesize that social recognition of prosocial behavior (self-serving behavior) weakens (strengthens) subsequent moral striving. In Study 1, we show that a prosocial act leads to less subsequent helpfulness when it was socially recognized as compared to a situation without social recognition. Conversely, when a self-serving act is socially recognized, it encourages subsequent helpfulness. In Study 2, we replicate the effect of social recognition on moral striving in a more elaborated experimental setting and with a larger participant sample. We again find that a socially recognized prosocial act leads to less subsequent helpfulness compared to an unrecognized prosocial act. Our results shed new light on the boundary conditions of moral balancing effects and underscore the view that these effects can be conceptualized as a dynamic of self-completion. KW - prosocial behavior KW - social influence KW - social recognition KW - self-regulation KW - moral balancing Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211327 SN - 1664-1078 VL - 11 ER - TY - JOUR A1 - Kunz, Tobias C. A1 - Götz, Ralph A1 - Gao, Shiqiang A1 - Sauer, Markus A1 - Kozjak-Pavlovic, Vera T1 - Using Expansion Microscopy to Visualize and Characterize the Morphology of Mitochondrial Cristae JF - Frontiers in Cell and Developmental Biology N2 - Mitochondria are double membrane bound organelles indispensable for biological processes such as apoptosis, cell signaling, and the production of many important metabolites, which includes ATP that is generated during the process known as oxidative phosphorylation (OXPHOS). The inner membrane contains folds called cristae, which increase the membrane surface and thus the amount of membrane-bound proteins necessary for the OXPHOS. These folds have been of great interest not only because of their importance for energy conversion, but also because changes in morphology have been linked to a broad range of diseases from cancer, diabetes, neurodegenerative diseases, to aging and infection. With a distance between opposing cristae membranes often below 100 nm, conventional fluorescence imaging cannot provide a resolution sufficient for resolving these structures. For this reason, various highly specialized super-resolution methods including dSTORM, PALM, STED, and SIM have been applied for cristae visualization. Expansion Microscopy (ExM) offers the possibility to perform super-resolution microscopy on conventional confocal microscopes by embedding the sample into a swellable hydrogel that is isotropically expanded by a factor of 4–4.5, improving the resolution to 60–70 nm on conventional confocal microscopes, which can be further increased to ∼ 30 nm laterally using SIM. Here, we demonstrate that the expression of the mitochondrial creatine kinase MtCK linked to marker protein GFP (MtCK-GFP), which localizes to the space between the outer and the inner mitochondrial membrane, can be used as a cristae marker. Applying ExM on mitochondria labeled with this construct enables visualization of morphological changes of cristae and localization studies of mitochondrial proteins relative to cristae without the need for specialized setups. For the first time we present the combination of specific mitochondrial intermembrane space labeling and ExM as a tool for studying internal structure of mitochondria. KW - Expansion microscopy KW - mitochondria KW - cristae KW - structured illumination microscope KW - ultrastructure Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208296 SN - 2296-634X VL - 8 ER - TY - JOUR A1 - Thorn, Simon A1 - Chao, Anne A1 - Bernhardt-Römermann, Markus A1 - Chen, Yan-Han A1 - Georgiev, Kostadin B. A1 - Heibl, Christoph A1 - Müller, Jörg A1 - Schäfer, Hanno A1 - Bässler, Claus T1 - Rare species, functional groups, and evolutionary lineages drive successional trajectories in disturbed forests JF - Ecology N2 - Following natural disturbances, additional anthropogenic disturbance may alter community recovery by affecting the occurrences of species, functional groups, and evolutionary lineages. However, our understanding of whether rare, common, or dominant species, functional groups, or evolutionary lineages are most strongly affected by an additional disturbance, particularly across multiple taxa, is limited. Here, we used a generalized diversity concept based on Hill numbers to quantify the community differences of vascular plants, bryophytes, lichens, wood‐inhabiting fungi, saproxylic beetles, and birds in a storm‐disturbed, experimentally salvage logged forest. Communities of all investigated species groups showed dissimilarities between logged and unlogged plots. Most species groups showed no significant changes in dissimilarities between logged and unlogged plots over the first seven years of succession, indicating a lack of community recovery. In general, the dissimilarities of communities were mainly driven by rare species. Convergence of dissimilarities occurred more often than divergence during the early stages of succession for rare species, indicating a major role in driving decreasing taxonomic dissimilarities between logged and unlogged plots over time. Trends in species dissimilarities only partially match the trends in dissimilarities of functional groups and evolutionary lineages, with little significant changes in successional trajectories. Nevertheless, common and dominant species contributed to a convergence of dissimilarities over time in the case of the functional dissimilarities of wood‐inhabiting fungi. Our study shows that salvage logging following disturbances can alter successional trajectories in early stages of forest succession following natural disturbances. However, community changes over time may differ remarkably in different taxonomic groups and are best detected based on taxonomic, rather than functional or phylogenetic dissimilarities. KW - wood-inhabiting fungi KW - birds KW - bryophytes KW - climate change KW - forest succession KW - Hill numbers KW - natural disturbances KW - salvage logging KW - saproxylic beetles KW - vascular plants Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212378 VL - 101 IS - 3 ER - TY - JOUR A1 - Chen, Xinyu A1 - Kudo, Takashi A1 - Lapa, Constantin A1 - Buck, Andreas A1 - Higuchi, Takahiro T1 - Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements JF - Journal of Neural Transmission N2 - The norepinephrine transporter (NET) is a major target for the evaluation of the cardiac sympathetic nerve system in patients with heart failure and Parkinson's disease. It is also used in the therapeutic applications against certain types of neuroendocrine tumors, as exemplified by the clinically used \(^{123/131}\)I-MIBG as theranostic single-photon emission computed tomography (SPECT) agent. With the development of more advanced positron emission tomography (PET) technology, more radiotracers targeting NET have been reported, with superior temporal and spatial resolutions, along with the possibility of functional and kinetic analysis. More recently, fluorine-18-labelled NET tracers have drawn increasing attentions from researchers, due to their longer radiological half-life relative to carbon-11 (110 min vs. 20 min), reduced dependence on on-site cyclotrons, and flexibility in the design of novel tracer structures. In the heart, certain NET tracers provide integral diagnostic information on sympathetic innervation and the nerve status. In the central nervous system, such radiotracers can reveal NET distribution and density in pathological conditions. Most radiotracers targeting cardiac NET-function for the cardiac application consistent of derivatives of either norepinephrine or MIBG with its benzylguanidine core structure, e.g. \(^{11}\)C-HED and \(^{18}\)F-LMI1195. In contrast, all NET tracers used in central nervous system applications are derived from clinically used antidepressants. Lastly, possible applications of NET as selective tracers over organic cation transporters (OCTs) in the kidneys and other organs controlled by sympathetic nervous system will also be discussed. KW - norepinephrine transporter KW - benzylguanidine KW - phenethylguanidine KW - antidepressant KW - organic cation transporter Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241148 VL - 127 ER - TY - JOUR A1 - Goettel, James T. A1 - Gao, Haopeng A1 - Dotzauer, Simon A1 - Braunschweig, Holger T1 - \(^{Me}\)CAAC=N\(^{-}\): A Cyclic (Alkyl)(Amino)Carbene Imino Ligand JF - Chemistry – A European Journal N2 - A cyclic (alkyl)(amino)carbene (CAAC) has been shown to react with a covalent azide similar to the Staudinger reaction. The reaction of \(^{Me}\)CAAC with trimethylsilyl azide afforded the N‐silylated 2‐iminopyrrolidine (\(^{Me}\)CAAC=NSiMe\(_{3}\)), which was fully characterized. This compound undergoes hydrolysis to afford the 2‐iminopyrrolidine and trimethylsiloxane which co‐crystallize as a hydrogen‐bonded adduct. The N‐silylated 2‐iminopyrrolidine was used to transfer the novel pyrrolidine‐2‐iminato ligand onto both main‐group and transition‐metal centers. The reaction of the tetrabromodiborane bis(dimethyl sulfide) adduct with two equivalents of \(^{Me}\)CAAC=NSiMe\(_{3}\) afforded the disubstituted diborane. The reaction of \(^{Me}\)CAAC=NSiMe\(_{3}\) with TiCl\(_{4}\) and CpTiCl\(_{3}\) afforded \(^{Me}\)CAAC=NTiCl\(_{3}\) and \(^{Me}\)CAAC=NTiCl\(_{2}\)Cp, respectively. KW - boron KW - carbenes KW - imide ligands KW - nitrogen ligands KW - titanium Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212662 VL - 26 IS - 5 ER - TY - JOUR A1 - Umstätter, Florian A1 - Domhan, Cornelius A1 - Hertlein, Tobias A1 - Ohlsen, Knut A1 - Mühlberg, Eric A1 - Kleist, Christian A1 - Zimmermann, Stefan A1 - Beijer, Barbro A1 - Klika, Karel D. A1 - Haberkorn, Uwe A1 - Mier, Walter A1 - Uhl, Philipp T1 - Vancomycin Resistance Is Overcome by Conjugation of Polycationic Peptides JF - Angewandte Chemie International Edition N2 - Multidrug‐resistant bacteria represent one of the biggest challenges facing modern medicine. The increasing prevalence of glycopeptide resistance compromises the efficacy of vancomycin, for a long time considered as the last resort for the treatment of resistant bacteria. To reestablish its activity, polycationic peptides were conjugated to vancomycin. By site‐specific conjugation, derivatives that bear the peptide moiety at four different sites of the antibiotic were synthesized. The most potent compounds exhibited an approximately 1000‐fold increased antimicrobial activity and were able to overcome the most important types of vancomycin resistance. Additional blocking experiments using d‐Ala‐d‐Ala revealed a mode of action beyond inhibition of cell‐wall formation. The antimicrobial potential of the lead candidate FU002 for bacterial infection treatments could be demonstrated in an in vivo study. Molecular imaging and biodistribution studies revealed that conjugation engenders superior pharmacokinetics. KW - antibiotics KW - bacterial resistance KW - glycopeptide antibiotics KW - peptide conjugates KW - vancomycin Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215550 VL - 59 IS - 23 SP - 8823 EP - 8827 ER - TY - JOUR A1 - Boelch, Sebastian Philipp A1 - Streck, Laura Elisa A1 - Plumhoff, Piet A1 - Konrads, Christian A1 - Gohlke, Frank A1 - Rueckl, Kilian T1 - Infection control and outcome of staged reverse shoulder arthroplasty for the management of shoulder infections JF - JSES International N2 - Background The treatment of septic arthritis, caused by either hematogenous seeding, injections, or surgery, can be challenging. Staged reverse shoulder arthroplasty (RSA) with temporary implantation of an antibiotic-loaded spacer is widely accepted but still discussed controversially. This study investigated the shoulder-specific bacterial spectrum, infection control rate, functional outcome, and infection-free survival rate after staged RSA in the mid- to long-term follow-up. It was hypothesized that staged RSA would show a high infection-free survival rate. Methods A total of 39 patients treated with staged RSA for primary septic arthritis (n = 8), secondary infection (n = 8), or periprosthetic infection (n = 23) were retrospectively included. The infection control rate was calculated based on cultures taken intraoperatively at spacer removal and RSA implantation. Infection-free survival was defined as no revision due to infection. The minimum follow-up period for functional outcome assessment was 2 years (n = 14; mean, 76 months; range, 31-128 months). Results Cutibacterium (26%) and coagulase-negative staphylococci (23%) were the predominant pathogens. The infection control rate was 90%. The cumulative infection-free survival rate was 91% after 128 months. Follow-up examinations showed a mean Constant score of 48 (range, 7-85), a mean QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score of 40.0 (range, 11.4-93.3), and a mean pain score of 1.6 (range, 0-7). Conclusion Staged RSA implantation was confirmed to be a reliable treatment option for primary, secondary, and periprosthetic infections of the shoulder. The infection control rate and infection-free survival rate are satisfactory. However, patients and surgeons must be aware of functional impairment even after successful treatment of infections. KW - shoulder infection KW - periprosthetic infection KW - two stage KW - spacer KW - reerse shoulder arthoplasty KW - shoulder arthroplasty KW - outcome Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230620 VL - 4 ER - TY - JOUR A1 - Ferber, Elena A1 - Gerhards, Julian A1 - Sauer, Miriam A1 - Krischke, Markus A1 - Dittrich, Marcus T. A1 - Müller, Tobias A1 - Berger, Susanne A1 - Fekete, Agnes A1 - Mueller, Martin J. T1 - Chemical Priming by Isothiocyanates Protects Against Intoxication by Products of the Mustard Oil Bomb JF - Frontiers in Plant Science N2 - In Brassicaceae, tissue damage triggers the mustard oil bomb i.e., activates the degradation of glucosinolates by myrosinases leading to a rapid accumulation of isothiocyanates at the site of damage. Isothiocyanates are reactive electrophilic species (RES) known to covalently bind to thiols in proteins and glutathione, a process that is not only toxic to herbivores and microbes but can also cause cell death of healthy plant tissues. Previously, it has been shown that subtoxic isothiocyanate concentrations can induce transcriptional reprogramming in intact plant cells. Glutathione depletion by RES leading to breakdown of the redox potential has been proposed as a central and common RES signal transduction mechanism. Using transcriptome analyses, we show that after exposure of Arabidopsis seedlings (grown in liquid culture) to subtoxic concentrations of sulforaphane hundreds of genes were regulated without depletion of the cellular glutathione pool. Heat shock genes were among the most highly up-regulated genes and this response was found to be dependent on the canonical heat shock factors A1 (HSFA1). HSFA1-deficient plants were more sensitive to isothiocyanates than wild type plants. Moreover, pretreatment of Arabidopsis seedlings with subtoxic concentrations of isothiocyanates increased resistance against exposure to toxic levels of isothiocyanates and, hence, may reduce the autotoxicity of the mustard oil bomb by inducing cell protection mechanisms. KW - autotoxicity KW - heat shock response KW - isothiocyanates KW - mustard oil bomb KW - reactive electrophilic species KW - redox homeostasis KW - sulforaphane Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207104 SN - 1664-462X VL - 11 ER - TY - JOUR A1 - Nees, Samuel A1 - Kupfer, Thomas A1 - Hofmann, Alexander A1 - Braunschweig, Holger T1 - Stabilisierung planarer Cyclopenten‐4‐yl‐Kationen durch Hyperkonjugation und π‐Delokalisierung JF - Angewandte Chemie N2 - Theoretischen Untersuchungen zufolge stellt das planare Cyclopenten-4-yl-Kation das energetisch ungünstigste C\(_{5}\)H\(_{7}\)\(^{+}\)-Isomer dar und ist am ehesten als klassisches Carbokation zu beschreiben, wobei dessen Existenz experimentell bislang noch nicht nachgewiesen werden konnte. Durch Umsetzung sterisch überfrachteter Alane vom Typ Cp\(^{R}\)AlBr\(_{2}\) mit AlBr3 ist uns nun die Isolierung zweier stabiler Derivate des Cyclopenten-4-yl-Kations gelungen. Untersuchungen zu deren (elektronischer) Struktur (XRD, QM) offenbarten planare Geometrien und starke Hyperkonjugationswechselwirkungen zwischen den C-Al-σ-Bindungen und dem unbesetzten p-Orbital der kationischen sp\(^{2}\)-Kohlenstoffzentren. Die Analyse der Molekülorbitale (MOs), der Anisotropie der induzierten Stromdichte (ACID) sowie verschiedener Aromatizitätsdeskriptoren deuten hierbei auf ein hohes Maß an Delokalisierung und π-Aromatizität in diesen Systemen hin, was einer klassischen Beschreibung grundlegend widerspricht. Unsere Cyclopenten-4-yl-Kationen gehören somit zu den wenigen Beispielen aromatischer Carbocyclen, in denen eine Delokalisierung der π-Elektronen über gesättigte sp\(^{3}\)-Kohlenstoffatome hinweg beobachtet wird. KW - ACID KW - Carbokationen KW - Cyclopenten-4-yl-Kation KW - Hyperkonjugation KW - π-Aromatizität Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218456 VL - 132 IS - 42 SP - 18971 EP - 18978 ER - TY - JOUR A1 - Cao, Liyu A1 - Steinborn, Michael A1 - Kunde, Wilfried A1 - Haendel, Barbara T1 - Action force modulates action binding: evidence for a multisensory information integration explanation JF - Experimental Brain Research N2 - Action binding refers to the observation that the perceived time of an action (e.g., a keypress) is shifted towards the distal sensory feedback (usually a sound) triggered by that action. Surprisingly, the role of somatosensory feedback for this phe-nomenon has been largely ignored. We fill this gap by showing that the somatosensory feedback, indexed by keypress peak force, is functional in judging keypress time. Specifically, the strength of somatosensory feedback is positively correlated with reported keypress time when the keypress is not associated with an auditory feedback and negatively correlated when the keypress triggers an auditory feedback. The result is consistent with the view that the reported keypress time is shaped by sensory information from different modalities. Moreover, individual differences in action binding can be explained by a sensory information weighting between somatosensory and auditory feedback. At the group level, increasing the strength of somatosensory feedback can decrease action binding to a level not being detected statistically. Therefore, a multisensory information integration account (between somatosensory and auditory inputs) explains action binding at both a group level and an individual level. KW - action binding KW - force KW - somatosensory feedback KW - multisensory processing Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232534 SN - 0014-4819 VL - 238 ER - TY - JOUR A1 - Urban, Lara A1 - Remmele, Christian W. A1 - Dittrich, Marcus A1 - Schwarz, Roland F. A1 - Müller, Tobias T1 - covRNA: discovering covariate associations in large-scale gene expression data JF - BMC Reserach Notes N2 - Objective The biological interpretation of gene expression measurements is a challenging task. While ordination methods are routinely used to identify clusters of samples or co-expressed genes, these methods do not take sample or gene annotations into account. We aim to provide a tool that allows users of all backgrounds to assess and visualize the intrinsic correlation structure of complex annotated gene expression data and discover the covariates that jointly affect expression patterns. Results The Bioconductor package covRNA provides a convenient and fast interface for testing and visualizing complex relationships between sample and gene covariates mediated by gene expression data in an entirely unsupervised setting. The relationships between sample and gene covariates are tested by statistical permutation tests and visualized by ordination. The methods are inspired by the fourthcorner and RLQ analyses used in ecological research for the analysis of species abundance data, that we modified to make them suitable for the distributional characteristics of both, RNA-Seq read counts and microarray intensities, and to provide a high-performance parallelized implementation for the analysis of large-scale gene expression data on multi-core computational systems. CovRNA provides additional modules for unsupervised gene filtering and plotting functions to ensure a smooth and coherent analysis workflow. KW - Multivariate analysis KW - Fourthcorner analysis KW - RLQ analysis KW - Transcriptomics KW - High-throughput data KW - Visualization KW - Ordination methods KW - RNA-Seq analysis KW - Microarray analysis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229258 VL - 13 ER - TY - JOUR A1 - Groma, Michaela A1 - Horst, Sarah A. A1 - Das, Sudip A1 - Huettel, Bruno A1 - Klepsch, Maximilian A1 - Rudel, Thomas A1 - Medina, Eva A1 - Fraunholz, Martin T1 - Identification of a Novel LysR-Type Transcriptional Regulator in Staphylococcus aureus That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection JF - mbio N2 - Staphylococcus aureus is a common cause of bacteremia that can lead to severe complications once the bacteria exit the bloodstream and establish infection in secondary organs. Despite its clinical relevance, little is known about the bacterial factors facilitating the development of these metastatic infections. Here, we used an S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) to identify genes that are critical for efficient bacterial colonization of secondary organs in a murine model of metastatic bloodstream infection. Our transposon screen identified a LysR-type transcriptional regulator (LTTR), which was required for efficient colonization of secondary organs such as the kidneys in infected mice. The critical role of LTTR in secondary organ colonization was confirmed using an isogenic mutant deficient in the expression of LTTR. To identify the set of genes controlled by LTTR, we used an S. aureus strain carrying the LTTR gene in an inducible expression plasmid. Gene expression analysis upon induction of LTTR showed increased transcription of genes involved in branched-chain amino acid biosynthesis, a methionine sulfoxide reductase, and a copper transporter as well as decreased transcription of genes coding for urease and components of pyrimidine nucleotides. Furthermore, we show that transcription of LTTR is repressed by glucose, is induced under microaerobic conditions, and required trace amounts of copper ions. Our data thus pinpoints LTTR as an important element that enables a rapid adaptation of S. aureus to the changing host microenvironment. IMPORTANCE Staphylococcus aureus is an important pathogen that can disseminate via the bloodstream and establish metastatic infections in distant organs. To achieve a better understanding of the bacterial factors facilitating the development of these metastatic infections, we used in this study a Staphylococcus aureus transposon mutant library in a murine model of intravenous infection, where bacteria first colonize the liver as the primary infection site and subsequently progress to secondary sites such as the kidney and bones. We identified a novel LysR-type transcriptional regulator (LTTR), which was specifically required by S. aureus for efficient colonization of secondary organs. We also determined the transcriptional activation as well as the regulon of LTTR, which suggests that this regulator is involved in the metabolic adaptation of S. aureus to the host microenvironment found in secondary infection sites. KW - Staphylococcus aureus KW - metabolic adaptation KW - secondary site infection KW - transcriptional regulation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230473 VL - 11 IS - 4 ER - TY - JOUR A1 - Weissenberger, Manuel A1 - Weissenberger, Manuela H. A1 - Wagenbrenner, Mike A1 - Heinz, Tizian A1 - Reboredo, Jenny A1 - Holzapfel, Boris M. A1 - Rudert, Maximilian A1 - Groll, Jürgen A1 - Evans, Christopher H. A1 - Steinert, Andre F. T1 - Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer JF - PLoS One N2 - Objective As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. Design Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX)9,transforming growth factor beta (TGFB) 1or bone morphogenetic protein (BMP) 2cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. Results Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenesSOX9,TGFB1andBMP2as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups (BMP2>TGFB1>SOX9). Conclusions Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factorsSOX9,TGFB1andBMP2. This technology may be harnessed for regeneration of specific zones of native cartilage upon damage. KW - stem cells KW - in vitro KW - chondrogenic differentiation KW - repair KW - chondrocytes KW - transplantation KW - stimulation KW - scaffolds KW - defects KW - therapy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230494 VL - 15 IS - 8 ER - TY - JOUR A1 - Tendera, Lukas A1 - Schaub, Thomas A1 - Krahfuss, Mirjam J. A1 - Kuntze‐Fechner, Maximilian W. A1 - Radius, Udo T1 - Large vs. Small NHC Ligands in Nickel(0) Complexes: The Coordination of Olefins, Ketones and Aldehydes at [Ni(NHC)\(_{2}\)] JF - European Journal of Inorganic Chemistry N2 - Investigations concerning the reactivity of Ni(0) complexes [Ni(NHC)\(_{2}\)] of NHCs (N‐heterocyclic carbene) of different steric demand, Mes\(_{2}\)Im (= 1,3‐dimesitylimidazoline‐2‐ylidene) and iPr\(_{2}\)Im (= 1,3‐diisopropyl‐imidazoline‐2‐ylidene), with olefins, ketones and aldehydes are reported. The reaction of [Ni(Mes\(_{2}\)Im)\(_{2}\)] 1 with ethylene or methyl acrylate afforded the complexes [Ni(Mes\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐C\(_{2}\)H\(_{4}\))] 3 and [Ni(Mes\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐(C,C)‐H\(_{2}\)C=CHCOOMe)] 4, as it was previously reported for [Ni\(_{2}\)(iPr\(_{2}\)Im)\(_{4}\)(µ‐(η\(^{2}\):η\(^{2}\))‐COD)] 2 as a source for [Ni(iPr\(_{2}\)Im)\(_{2}\)]. In contrast to 2, complex 1 does not react with sterically more demanding olefins such as tetramethylethylene, 1,1‐diphenylethylene and cyclohexene. The reaction of [Ni(NHC)\(_{2}\)] with more π‐acidic ketones or aldehydes led to formation of complexes with side‐on η\(^{2}\)‐(C,O)‐coordinating ligands: [Ni(iPr\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CH\(^{t}\)Bu)] 5, [Ni(iPr\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CHPh)] 6, [Ni(iPr\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CMePh)] 7, [Ni(iPr\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CPh\(_{2}\))] 8, [Ni(iPr\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=C(4‐F‐C\(_{6}\)H\(_{4}\))\(_{2}\))] 9, [Ni(iPr\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=C(OMe)(CF\(_{3}\)))] 10 and [Ni(Mes\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CHPh)] 11, [Ni(Mes\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CH(CH(CH\(_{3}\))\(_{2}\)))] 12, [Ni(Mes\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CH(4‐NMe\(_{2}\)‐C\(_{6}\)H\(_{4}\)))] 13, [Ni(Mes\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CH(4‐OMe‐C\(_{6}\)H\(_{4}\)))] 14, [Ni(Mes\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=CPh\(_{2}\))] 15 and [Ni(Mes\(_{2}\)Im)\(_{2}\)(η\(^{2}\)‐O=C(4‐F‐C\(_{6}\)H\(_{4}\))\(_{2}\))] 16. The reaction of 1 and 2 with these simple aldehydes and ketones does not lead to a significantly different outcome, but NHC ligand rotation is hindered for the Mes\(_{2}\)Im complexes 3, 4 and 11–16 according to NMR spectroscopy. The solid‐state structures of 3, 4, 11 and 12 reveal significantly larger C\(_{NHC}\)‐Ni‐C\(_{NHC}\) angles in the Mes\(_{2}\)Im complexes compared to the iPr\(_{2}\)Im complexes. As electron transfer in d\(^{8}\)‐ (or d\(^{10}\)‐) ML\(_{2}\) complexes to π‐acidic ligands depends on the L–M–L bite angle, the different NHCs lead thus to a different degree of electron transfer and activation of the olefin, aldehyde or ketone ligand, i.e., [Ni(iPr\(_{2}\)Im)\(_{2}\)] is the better donor to these π‐acidic ligands. Furthermore, we identified two different side products from the reaction of 1 with benzaldehyde, trans‐[Ni(Mes\(_{2}\)Im)\(_{2}\)H(OOCPh)] 17 and [Ni\(_{2}\)(Mes\(_{2}\)Im)\(_{2}\)(µ\(_{2}\)‐CO)(µ\(_{2}\)‐η\(^{2}\)‐C,O‐PhCOCOPh)] 18, which indicate that radical intermediates and electron transfer processes might be of importance in the reaction of 1 with aldehydes and ketones. KW - Nickel Complexes KW - N‐Heterocyclic Carbenes KW - NHC Complexes KW - Olefin Complexes KW - Aldehyde Complexes Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216058 VL - 2020 IS - 33 SP - 3194 EP - 3207 ER - TY - JOUR A1 - Hock, Andreas A1 - Werner, Luis A1 - Riethmann, Melanie A1 - Radius, Udo T1 - Bis‐NHC Aluminium and Gallium Dihydride Cations [(NHC)\(_{2}\)EH\(_{2}\)]\(^{+}\) (E = Al, Ga) JF - European Journal of Inorganic Chemistry N2 - The NHC alane and gallane adducts (NHC)·AlH\(_{2}\)I (NHC = Me\(_{2}\)Im\(^{Me}\) 7, iPr\(_{2}\)Im 8, iPr\(_{2}\)Im\(^{Me}\) 9) and (NHC)·GaH\(_{2}\)I (NHC = Me\(_{2}\)Im\(^{Me}\) 10, iPr\(_{2}\)Im\(^{Me}\) 11, Dipp\(_{2}\)Im 12; R\(_{2}\)Im = 1,3‐di‐organyl‐imidazolin‐2‐ylidene; Dipp = 2,6‐diisopropylphenyl; iPr = isopropyl; Me\(_{2}\)Im\(^{Me}\) = 1,3,4,5‐tetra‐methyl‐imidazolin‐2‐ylidene) were prepared either by the simple yet efficient reaction of the NHC adduct (NHC)·AlH\(_{3}\) with elemental iodine or by the treatment of (NHC)·GaH\(_{3}\) with an excess of methyl iodide at room temperature. The reaction of one equivalent of the group 13 NHC complexes with an additional equivalent of the corresponding NHC afforded cationic aluminium and gallium hydrides [(NHC)\(_{2}\)·AlH\(_{2}\)]\(^{+}\)I− (NHC = Me\(_{2}\)Im\(^{Me}\) 13, iPr\(_{2}\)Im 14, iPr\(_{2}\)Im\(^{Me}\) 15) and [(NHC)\(_{2}\)·GaH\(_{2}\)]\(^{+}\)I− (NHC = Me\(_{2}\)Im\(^{Me}\) 16, iPr\(_{2}\)Im\(^{Me}\) 17) and the normal and abnormal NHC coordinated compound [(Dipp\(_{2}\)Im)·GaH\(_{2}\)(aDipp\(_{2}\)Im)]+I− 18. Compounds 7–18 were isolated and characterized by means of elemental analysis, IR and multinuclear NMR spectroscopy and by X‐ray diffraction of the compounds 7, 9, 10, 15, 16 and 18. KW - aluminium KW - cations KW - Gallium KW - main group elements KW - heterocyclic carbenes Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217928 VL - 2020 IS - 42 SP - 4015 EP - 4023 ER - TY - JOUR A1 - Liu, Xiaocui A1 - Ming, Wenbo A1 - Friedrich, Alexandra A1 - Marder, Todd B. T1 - Kupfer‐katalysierte Triborierung terminaler Alkine mit B2pin2: Effiziente Synthese von 1,1,2‐Triborylalkenen JF - Angewandte Chemie N2 - Wir berichten über die katalytische Triborierung terminaler Alkine mit B\(_2\)pin\(_2\) (Bis‐(pinakolato)‐dibor) unter Verwendung von einfach zugänglichem Cu(OAc)\(_2\) und P\(^n\)Bu\(_3\). Verschiedene 1,1,2‐Triborylalkene, eine Verbindungsklasse mit potentieller Funktion als Matrix‐Metallo‐Proteinase(MMP‐2)‐Inhibitor, werden direkt in mäßigen bis guten Ausbeuten erhalten. Das Verfahren zeichnet sich durch milde Reaktionsbedingungen, ein breites Substratspektrum und eine gute Verträglichkeit gegenüber funktionellen Gruppen aus. Diese Cu‐katalysierte Reaktion kann im Gramm‐Maßstab durchgeführt werden und liefert die entsprechenden 1,1,2‐Triborylalkene in mäßigen Ausbeuten. Die Verwendung solcher Verbindungen wird anhand weiterer Transformationen der C−B‐Bindungen zur Darstellung eines geminalen Dihalogenborylalkens (F, Cl, Br), eines Monohalogendiborylalkens (Cl, Br) und eines trans‐Diaryldiborylalkens demonstriert, welche bedeutende Synthesebausteine darstellen und bisher nur schwer zugänglich waren. KW - Boronatester KW - Borylierung KW - Diborierung KW - Halogenierung KW - Kreuzkupplungen Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219699 VL - 132 IS - 1 ER - TY - JOUR A1 - Petrov, Ivan A1 - Gentschev, Ivaylo A1 - Vyalkova, Anna A1 - Elashry, Mohamed I. A1 - Klymiuk, Michele C. A1 - Arnhold, Stefan A1 - Szalay, Aladar A. T1 - Canine Adipose-Derived Mesenchymal Stem Cells (cAdMSCs) as a "Trojan Horse" in Vaccinia Virus Mediated Oncolytic Therapy against Canine Soft Tissue Sarcomas JF - Viruses N2 - Several oncolytic viruses (OVs) including various human and canine adenoviruses, canine distemper virus, herpes-simplex virus, reovirus, and members of the poxvirus family, such as vaccinia virus and myxoma virus, have been successfully tested for canine cancer therapy in preclinical and clinical settings. The success of the cancer virotherapy is dependent on the ability of oncolytic viruses to overcome the attacks of the host immune system, to preferentially infect and lyse cancer cells, and to initiate tumor-specific immunity. To date, several different strategies have been developed to overcome the antiviral host defense barriers. In our study, we used canine adipose-derived mesenchymal stem cells (cAdMSCs) as a “Trojan horse” for the delivery of oncolytic vaccinia virus Copenhagen strain to achieve maximum oncolysis against canine soft tissue sarcoma (CSTS) tumors. A single systemic administration of vaccinia virus-loaded cAdMSCs was found to be safe and led to the significant reduction and substantial inhibition of tumor growth in a CSTS xenograft mouse model. This is the first example that vaccinia virus-loaded cAdMSCs could serve as a therapeutic agent against CSTS tumors. KW - oncolytic virus KW - cancer KW - vaccinia virus KW - canine cancer cell lines KW - canine adipose-derived mesenchymal stem cells (cAdMSCs) KW - canine soft tissue sarcoma (CSTS) KW - canine cancer therapy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236007 VL - 12 IS - 7 ER - TY - JOUR A1 - Schmidt, Uwe A1 - Werner, Luis A1 - Arrowsmith, Merle A1 - Deissenberger, Andrea A1 - Hermann, Alexander A1 - Hofmann, Alexander A1 - Ullrich, Stefan A1 - Mattock, James D. A1 - Vargas, Alfredo A1 - Braunschweig, Holger T1 - Trans‐selektive Dihydroborierung eines cis‐Diborens durch Insertion: Synthese eines linearen sp\(^3\)‐sp\(^2\)‐sp\(^3\)‐Triborans und anschließende Kationisierung JF - Angewandte Chemie N2 - Die Reaktion zwischen Aryl‐ und Amino(dihydro)boranen und Dibora[2]ferrocenophan 1 führt zur Bildung von 1,3‐trans‐Dihydrotriboranen durch formale Hydrierung und Insertion eines Borylens in die B=B Doppelbindung. Die Aryltriboran‐Derivate unterliegen einer reversiblen Photoisomerisierung zugunsten eines cis‐1,2‐μ‐H‐3‐Hydrotriborans, während eine Hydridabstraktion zu kationischen Triboranen führt, welche die ersten doppelt basenstabilisierten B\(_3\)H\(_4\)\(^+\)‐Analoga darstellen. KW - Diboren KW - Hydroborierung KW - Kation KW - Photoisomerisierung KW - Triboran Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219713 VL - 132 IS - 1 ER - TY - JOUR A1 - Schmidt, Uwe A1 - Werner, Luis A1 - Arrowsmith, Merle A1 - Deissenberger, Andrea A1 - Hermann, Alexander A1 - Hofmann, Alexander A1 - Ullrich, Stefan A1 - Mattock, James D. A1 - Vargas, Alfredo A1 - Braunschweig, Holger T1 - trans-Selective Insertional Dihydroboration of a cis-Diborene: Synthesis of Linear sp\(^3\)-sp\(^2\)-sp\(^3\)-Triboranes and Subsequent Cationization JF - Angewandte Chemie International Edition N2 - The reaction of aryl‐ and amino(dihydro)boranes with dibora[2]ferrocenophane 1 leads to the formation 1,3‐trans ‐dihydrotriboranes by formal hydrogenation and insertion of a borylene unit into the B=B bond. The aryltriborane derivatives undergo reversible photoisomerization to the cis ‐1,2‐μ‐H‐3‐hydrotriboranes, while hydride abstraction affords cationic triboranes, which represent the first doubly base‐stabilized B3H4\(^+\) analogues. KW - cations KW - hydroboration KW - photoisomerization KW - triboranes KW - diborenes Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208090 VL - 59 IS - 1 ER - TY - JOUR A1 - Hermann, Alexander A1 - Fantuzzi, Felipe A1 - Arrowsmith, Merle A1 - Zorn, Theresa A1 - Krummenacher, Ivo A1 - Ritschel, Benedikt A1 - Radacki, Krzysztof A1 - Engels, Bernd A1 - Braunschweig, Holger T1 - Oxidation, Coordination, and Nickel-Mediated Deconstruction of a Highly Electron-Rich Diboron Analogue of 1,3,5-Hexatriene JF - Angewandte Chemie, International Edition N2 - The reductive coupling of an N-heterocyclic carbene (NHC) stabilized (dibromo)vinylborane yields a 1,2-divinyl- diborene, which, although isoelectronic to a 1,3,5-triene, displays no extended p conjugation because of twisting of the C\(_2\)B\(_2\)C\(_2\) chain. While this divinyldiborene coordinates to copper(I) and platinum(0) in an η\(^2\)-B\(_2\) and η\(^4\)-C\(_2\)B\(_2\) fashion, respectively, it undergoes a complex rearrangement to an η\(^4\)-1,3-diborete upon complexation with nickel(0). KW - boron KW - diborenes KW - carbenes KW - conjugation KW - density-functional calculations KW - rearrangements KW - structure elucidation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240652 VL - 59 IS - 36 ER - TY - JOUR A1 - Wirthensohn, Raphael A1 - Finze, Maik T1 - The crystal structure of trimethylsulfonium tris(trifluoromethylsulfonyl)methanide, C\(_7\)H\(_9\)F\(_9\)O\(_6\)S\(_4\) JF - Zeitschrift für Kristallographie - New Crystal Structures N2 - C\(_7\)H\(_9\)F\(_9\)O\(_6\)S\(_4\), orthorhombic, P2\(_1\)2\(_1\)2\(_1\) (no. 19), a = 8.80180(10) Å, b= 10.96580(10) Å, c = 16.91360(10) Å,V= 1632.48(3) Å\(^3\), Z= 4, R\(_{gt}\)(F) = 0.0222, wR\(_{ref}\)(F\(^2\)) = 0.0604, T = 100 K. KW - chemistry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231358 VL - 236 IS - 2 ER - TY - JOUR A1 - Emmert, Marcel A1 - Heß, Konrad A1 - Gräb, Patrick A1 - Geidel, Ekkehard T1 - Experiments to Introduce Students into the Temperature Dependence of the Reaction Rate JF - World Journal of Chemical Education N2 - It is a challenge in chemical education to understand basic principles of chemical reaction kinetics on an experimental basis because of the relatively extensive experimental setup and the often time-consuming measurement series. This contribution offers an introduction into the field of the temperature dependence of reaction rate with easy-to-use experiments. Data logging systems have been used to get sufficient data-sets to evaluate different measurements in reaction kinetics. Several experiments were designed for practical courses in chemistry, which allow students to derive the simple van‘t Hoff rule on the one hand. On the other hand, the Arrhenius equation can only be derived on the basis of experimental data with the help of information from collision theory and Maxwell-Boltzmann distribution. KW - temperature dependence of reaction rate KW - van‘t Hoff rule KW - Arrhenius equation KW - ow-cost photometer Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229993 VL - 8 IS - 2 ER - TY - JOUR A1 - Abdelhameed, Reda F. A. A1 - Eltamany, Enas E. A1 - Hal, Dina M. A1 - Ibrahim, Amany K. A1 - AboulMagd, Asmaa M. A1 - Al-Warhi, Tarfah A1 - Youssif, Khayrya A. A1 - Abd El-kader, Adel M. A1 - Hassanean, Hashim A. A1 - Fayez, Shaimaa A1 - Bringmann, Gerhard A1 - Ahmed, Safwat A. A1 - Abdelmohsen, Usama Ramadan T1 - New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies JF - Marine Drugs N2 - Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC\(_{50}\) values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC\(_{50}\) 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents. KW - LC-HRESIMS KW - Holothuria spinifera KW - cerebrosides KW - molecular docking KW - cytotoxicity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211089 SN - 1660-3397 VL - 18 IS - 8 ER - TY - JOUR A1 - Scheitl, Carolin P. M. A1 - Lange, Sandra A1 - Höbartner, Claudia T1 - New deoxyribozymes for the native ligation of RNA JF - Molecules N2 - Deoxyribozymes (DNAzymes) are small, synthetic, single-stranded DNAs capable of catalysing chemical reactions, including RNA ligation. Herein, we report a novel class of RNA ligase deoxyribozymes that utilize 5’-adenylated RNA (5’-AppRNA) as the donor substrate, mimicking the activated intermediates of protein-catalyzed RNA ligation. Four new DNAzymes were identified by in vitro selection from an N40 random DNA library and were shown to catalyze the intermolecular linear RNA-RNA ligation via the formation of a native 3’-5’-phosphodiester linkage. The catalytic activity is distinct from previously described RNA-ligating deoxyribozymes. Kinetic analyses revealed the optimal incubation conditions for high ligation yields and demonstrated a broad RNA substrate scope. Together with the smooth synthetic accessibility of 5’-adenylated RNAs, the new DNA enzymes are promising tools for the protein-free synthesis of long RNAs, for example containing precious modified nucleotides or fluorescent labels for biochemical and biophysical investigations. KW - RNA ligation KW - DNA catalysis KW - in vitro selection KW - Deoxyribozyme Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-210405 VL - 25 IS - 16 ER - TY - JOUR A1 - Renner, Rebecca A1 - Stolte, Matthias A1 - Würthner, Frank T1 - Self-Assembly of bowl-shaped naphthalimide-annulated corannulene JF - ChemistryOpen N2 - The self-assembly of a bowl-shaped naphthalimide-annulated corannulene of high solubility has been studied in a variety of solvents by NMR and UV/Vis spectroscopy. Evaluation by the anti-cooperative K\(_2\)-K model revealed the formation of supramolecular dimers of outstanding thermodynamic stability. Further structural proof for the almost exclusive formation of dimers over extended aggregates is demonstrated by atomic force microscopy (AFM) and diffusion ordered spectroscopy (DOSY) measurements as well as by theoretical calculations. Thus, herein we present the first report of a supramolecular dimer of an annulated corannulene derivative in solution and discuss its extraordinarily high thermodynamic stability with association constants up to > 10\(^6\)M\(^-\) \(^1\) in methylcyclohexane, which is comparable to the association constants given for planar phthalocyanine and perylene bisimide dyes. KW - corannulene KW - π-π-interactions KW - aelf-assembly KW - aggregation KW - supramolecular chemistry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204396 VL - 9 IS - 1 ER - TY - JOUR A1 - Maghami, Mohammad Ghaem A1 - Dey, Surjendu A1 - Lenz, Ann-Kathrin A1 - Höbartner, Claudia T1 - Repurpsing Antiviral Drugs for Orthogonal RNA-Catalyzed Labeling JF - Angewandte Chemie, International Edition N2 - In vitro selected ribozymes are promising tools for site-specific labeling of RNA. Previously known nucleic acid catalysts attached fluorescently labeled adenosine or guanosine derivatives through 2’,5’-branched phosphodiester bonds to the RNA of interest. Herein, we report new ribozymes that use orthogonal substrates, derived from the antiviral drug tenofovir, and attach bioorthogonal functional groups, as well as affinity handles and fluorescent reporter units through a hydrolytically more stable phosphonate ester linkage. The tenofovir transferase ribozymes were identified by in vitro selection and are orthogonal to nucleotide transferase ribozymes. As genetically encodable functional RNAs, these ribozymes may be developed for potential cellular applications. The orthogonal ribozymes addressed desired target sites in large RNAs in vitro, as shown by fluorescent labeling of E. coli 16S and 23S RNAs in total cellular RNA. KW - Antiviral nucleoside analogues KW - in vitro selection KW - ribozymes KW - site-specific RNA labeling KW - tenofovir Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205552 VL - 59 ER - TY - JOUR A1 - Schlosser, Julika A1 - Cibulka, Radek A1 - Groß, Philipp A1 - Ihmels, Heiko A1 - Mohrschladt, Christian J. T1 - Visible‐Light‐Induced Di‐\(\pi\)‐Methane Rearrangement of Dibenzobarrelene Derivatives JF - ChemPhotoChem N2 - It is demonstrated that the di‐\(\pi\)‐methane (DPM) rearrangement of carbonyl‐substituted dibenzobarrelene (9,10‐dihydro‐9,10‐ethenoanthracene) derivatives is induced by visible‐light‐induced triplet photosensitization with Ir(ppy)\(_{3}\), Ir(dFppy)\(_{3}\) or 1‐butyl‐7,8‐dimethoxy‐3‐methylalloxazine as catalysts, whereas derivatives that lack carbonyl substituents are photoinert under these conditions. Notably, the products are formed almost quantitatively. KW - dibenzosemibullvalenes KW - di-\(\pi\)-methane rearrangement KW - ethenoanthracenes KW - photocatalysis KW - photosensitization Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212633 VL - 4 IS - 2 SP - 132 EP - 137 ER - TY - JOUR A1 - Schindler, Dorothee A1 - Gil‐Sepulcre, Marcos A1 - Lindner, Joachim O. A1 - Stepanenko, Vladimir A1 - Moonshiram, Dooshaye A1 - Llobet, Antoni A1 - Würthner, Frank T1 - Efficient Electrochemical Water Oxidation by a Trinuclear Ru(bda) Macrocycle Immobilized on Multi‐Walled Carbon Nanotube Electrodes JF - Advanced Energy Materials N2 - Catalytic water splitting is a viable process for the generation of renewable fuels. Here it is reported for the first time that a trinuclear supramolecular Ru(bda) (bda: 2,2′‐bipyridine‐6,6′‐dicarboxylate) catalyst, anchored on multi‐walled carbon nanotubes and subsequently immobilized on glassy carbon electrodes, shows outstanding performance in heterogeneous water oxidation. Activation of the catalyst on anodes by repetitive cyclic voltammetry (CV) scans results in a catalytic current density of 186 mA cm\(^{−2}\) at a potential of 1.45 V versus NHE. The activated catalyst performs water oxidation at an onset overpotential of 330 mV. The remarkably high stability of the hybrid anode is demonstrated by X‐ray absorption spectroscopy and electrochemically, revealing the absence of any degradation after 1.8 million turnovers. Foot of the wave analysis of CV data of activated electrodes with different concentrations of catalyst indicates a monomolecular water nucleophilic attack mechanism with an apparent rate constant of TOFmax (turnover frequency) of 3200 s\(^{−1}\). KW - electrocatalysis KW - heterogeneous catalysis KW - renewable fuels KW - ruthenium bda complexes KW - water splitting Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218381 VL - 10 IS - 43 ER - TY - JOUR A1 - Liu, Xiaocui A1 - Ming, Wenbo A1 - Luo, Xiaoling A1 - Friedrich, Alexandra A1 - Maier, Jan A1 - Radius, Udo A1 - Santos, Webster L. A1 - Marder, Todd B. T1 - Regio‐ and Stereoselective Synthesis of 1,1‐Diborylalkenes via Brønsted Base‐Catalyzed Mixed Diboration of Alkynyl Esters and Amides with BpinBdan JF - European Journal of Organic Chemistry N2 - The NaOtBu‐catalyzed mixed 1,1‐diboration of terminal alkynes using the unsymmetrical diboron reagent BpinBdan (pin = pinacolato; dan = 1,8‐diaminonaphthalene) proceeds in a regio‐ and stereoselective fashion affording moderate to high yields of 1,1‐diborylalkenes bearing orthogonal boron protecting groups. It is applicable to gram‐scale synthesis without loss of yield or selectivity. The mixed 1,1‐diborylalkene products can be utilized in Suzuki–Miyaura cross‐coupling reactions which take place selectivly at the C–B site. DFT calculations suggest the NaOtBu‐catalyzed mixed 1,1‐diboration of alkynes occurs through deprotonation of the terminal alkyne, stepwise addition of BpinBdan to the terminal carbon followed by protonation with tBuOH. Experimentally observed selective formation of (Z)‐diborylalkenes is supported by our theoretical studies. KW - boronate esters KW - borylation KW - cross‐coupling KW - synthesis design KW - structure elucidation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214728 VL - 2020 IS - 13 SP - 1941 EP - 1946 ER - TY - JOUR A1 - Liaqat, Anam A1 - Stiller, Carina A1 - Michel, Manuela A1 - Sednev, Maksim V. A1 - Höbartner, Claudia T1 - N\(^6\)-Isopentenyladenosine in RNA Determines the Cleavage Site of Endonuclease Deoxyribozymes JF - Angewandte Chemie International Edition N2 - RNA-cleaving deoxyribozymes can serve as selective sensors and catalysts to examine the modification state of RNA. However, site-specific endonuclease deoxyribozymes that selectively cleave posttranscriptionally modified RNA are extremely rare and their specificity over unmodified RNA is low. In this study, we report that the native tRNA modification N\(^6\)-isopentenyladenosine (i\(^6\)A) strongly enhances the specificity and has the power to reconfigure the active site of an RNA-cleaving deoxyribozyme. Using in vitro selection, we identified a DNA enzyme that cleaves i\(^6\)A-modified RNA at least 2500-fold faster than unmodified RNA. Another deoxyribozyme shows unique and unprecedented behaviour by shifting its cleavage site in the presence of the i\(^6\)A RNA modification. Together with deoxyribozymes that are strongly inhibited by i\(^6\)A, these results highlight intricate ways of modulating the catalytic activity of DNA by posttranscriptional RNA modifications. KW - Deoxyribozymes KW - Epitranscriptomics KW - in vitro selection KW - RNA modification KW - site-specific RNA cleavage Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212121 ET - Early View ER - TY - JOUR A1 - Rauch, Florian A1 - Endres, Peter A1 - Friedrich, Alexandra A1 - Sieh, Daniel A1 - Hähnel, Martin A1 - Krummenacher, Ivo A1 - Braunschweig, Holger A1 - Finze, Maik A1 - Ji, Lei A1 - Marder, Todd B. T1 - An Iterative Divergent Approach to Conjugated Starburst Borane Dendrimers JF - Chemistry – A European Journal N2 - Using a new divergent approach, conjugated triarylborane dendrimers were synthesized up to the 2nd generation. The synthetic strategy consists of three steps: 1) functionalization, via iridium catalyzed C−H borylation; 2) activation, via fluorination of the generated boronate ester with K[HF\(_{2}\)] or [N(nBu\(_{4}\))][HF\(_{2}\)]; and 3) expansion, via reaction of the trifluoroborate salts with aryl Grignard reagents. The concept was also shown to be viable for a convergent approach. All but one of the conjugated borane dendrimers exhibit multiple, distinct and reversible reduction potentials, making them potentially interesting materials for applications in molecular accumulators. Based on their photophysical properties, the 1st generation dendrimers exhibit good conjugation over the whole system. However, the conjugation does not increase further upon expansion to the 2nd generation, but the molar extinction coefficients increase linearly with the number of triarylborane subunits, suggesting a potential application as photonic antennas. KW - density functional calculations KW - electron storage KW - luminescence KW - redox KW - triarylborane Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218345 VL - 26 IS - 57 SP - 12951 EP - 12963 ER - TY - JOUR A1 - Rohmann, Jessica L. A1 - Huo, Shufan A1 - Sperber, Pia S. A1 - Piper, Sophie K. A1 - Rosendaal, Frits R. A1 - Heuschmann, Peter U. A1 - Endres, Matthias A1 - Liman, Thomas G. A1 - Siegerink, Bob T1 - Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke JF - Journal of Thrombosis and Haemostasis N2 - Background Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post‐stroke exists. Objectives Coagulation factors XII, XI, and VIII (FXII, FXI, and FVIII) have been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. Patients/Methods In the Prospective Cohort with Incident Stroke Berlin (PROSCIS‐B) study, we followed participants aged 18 and older for 3 years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction, or all‐cause mortality. We compared high coagulation factor activity levels to normal and low levels and also analyzed activities as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint. Results In total, 94 events occurred in 576 included participants, resulting in an absolute rate of 6.6 events per 100 person‐years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR = 2.05, 95% confidence interval [CI] 1.28–3.29). High FXI activity was also associated with a higher hazard (HR = 1.80, 95% CI 1.09–2.98), though high FXII activity was not (HR = 0.86, 95% CI 0.49–1.51). Continuous analyses yielded similar results. Conclusions In our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the 3‐year period after first ischemic stroke. KW - coagulation KW - factor VIII KW - factor XI KW - factor XII KW - ischemic stroke Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217877 VL - 18 IS - 12 SP - 3316 EP - 3324 ER - TY - JOUR A1 - Nees, Samuel A1 - Kupfer, Thomas A1 - Hofmann, Alexander A1 - Braunschweig, Holger T1 - Planar Cyclopenten‐4‐yl Cations: Highly Delocalized π Aromatics Stabilized by Hyperconjugation JF - Angewandte Chemie International Edition N2 - Theoretical studies predicted the planar cyclopenten‐4‐yl cation to be a classical carbocation, and the highest‐energy isomer of C\(_{5}\)H\(_{7}\)\(^{+}\). Hence, its existence has not been verified experimentally so far. We were now able to isolate two stable derivatives of the cyclopenten‐4‐yl cation by reaction of bulky alanes Cp\(^{R}\)AlBr\(_{2}\) with AlBr3. Elucidation of their (electronic) structures by X‐ray diffraction and quantum chemistry studies revealed planar geometries and strong hyperconjugation interactions primarily from the C−Al σ bonds to the empty p orbital of the cationic sp\(^{2}\) carbon center. A close inspection of the molecular orbitals (MOs) and of the anisotropy of current (induced) density (ACID), as well as the evaluation of various aromaticity descriptors indicated distinct aromaticity for these cyclopenten‐4‐yl derivatives, which strongly contrasts the classical description of this system. Here, strong delocalization of π electrons spanning the whole carbocycle has been verified, thus providing rare examples of π aromaticity involving saturated sp\(^{3}\) carbon atoms. KW - ACID KW - carbocations KW - cyclopenten-4-yl cation KW - hyperconjugation KW - π aromaticity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218358 VL - 59 IS - 42 SP - 18809 EP - 18815 ER - TY - JOUR A1 - Humberg, Alexander A1 - Fortmann, Ingmar A1 - Siller, Bastian A1 - Kopp, Matthias Volkmar A1 - Herting, Egbert A1 - Göpel, Wolfgang A1 - Härtel, Christoph T1 - Preterm birth and sustained inflammation: consequences for the neonate JF - Seminars in Immunopathology N2 - Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome. KW - preterm infants KW - sustained inflammation KW - sepsis KW - microbiome KW - neurocognitive outcome KW - chronic pulmonary insufficiency of prematurity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235019 SN - 1863-2297 VL - 42 ER - TY - JOUR A1 - Esken, Jens A1 - Goris, Tobias A1 - Gadkari, Jennifer A1 - Bischler, Thorsten A1 - Förstner, Konrad U. A1 - Sharma, Cynthia M. A1 - Diekert, Gabriele A1 - Schubert, Torsten T1 - Tetrachloroethene respiration in Sulfurospirillum species is regulated by a two‐component system as unraveled by comparative genomics, transcriptomics, and regulator binding studies JF - MicrobiologyOpen N2 - Energy conservation via organohalide respiration (OHR) in dehalogenating Sulfurospirillum species is an inducible process. However, the gene products involved in tetrachloroethene (PCE) sensing and signal transduction have not been unambiguously identified. Here, genome sequencing of Sulfurospirillum strains defective in PCE respiration and comparative genomics, which included the PCE‐respiring representatives of the genus, uncovered the genetic inactivation of a two‐component system (TCS) in the OHR gene region of the natural mutants. The assumption that the TCS gene products serve as a PCE sensor that initiates gene transcription was supported by the constitutive low‐level expression of the TCS operon in fumarate‐adapted cells of Sulfurospirillum multivorans. Via RNA sequencing, eight transcriptional units were identified in the OHR gene region, which includes the TCS operon, the PCE reductive dehalogenase operon, the gene cluster for norcobamide biosynthesis, and putative accessory genes with unknown functions. The OmpR‐family response regulator (RR) encoded in the TCS operon was functionally characterized by promoter‐binding assays. The RR bound a cis‐regulatory element that contained a consensus sequence of a direct repeat (CTATW) separated by 17 bp. Its location either overlapping the −35 box or 50 bp further upstream indicated different regulatory mechanisms. Sequence variations in the regulator binding sites identified in the OHR gene region were in accordance with differences in the transcript levels of the respective gene clusters forming the PCE regulon. The results indicate the presence of a fine‐tuned regulatory network controlling PCE metabolism in dehalogenating Sulfurospirillum species, a group of metabolically versatile organohalide‐respiring bacteria. KW - genomics KW - organohalide respiration KW - RNA sequencing KW - tetrachloroethene KW - transcriptomics KW - two‐component system Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225754 VL - 9 IS - 12 ER -